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use of the odd-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice.in humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. in laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. recently a mouse model was generated in which a chimeric protein consisting of hif-1α oxygen-dependent degradation domain (odd) fused to luciferase was ubiquitously expressed in all tissues. hypoxic stress leads to the accumulation of odd-luciferase in the tissues of t ...201121479246
erbb3 ablation impairs pi3k/akt-dependent mammary tumorigenesis.the erbb receptor family member erbb3 has been implicated in breast cancer growth, but it has yet to be determined whether its disruption is therapeutically valuable. in a mouse model of mammary carcinoma driven by the polyomavirus middle t (pyvmt) oncogene, the erbb2 tyrosine kinase inhibitor lapatinib reduced the activation of erbb3 and akt as well as tumor cell growth. in this phosphatidylinositol-3 kinase (pi3k)-dependent tumor model, erbb2 is part of a complex containing pyvmt, p85 (pi3k), ...201121482676
measles virus antigens in breast cancer.breast cancer (bc) is the most common cancer in women in western countries, showing a bimodal age distribution with peaks at 50 and 70 years. multiple factors are encountered in the etiology of bc, including hereditary and hormonal causes. a few viruses, including mmtv, ebv and hpv have been reported to be associated with bc. this group previously described the presence of the measles virus (mv) in biopsies of patients with hodgkin's lymphoma. the present study explored mv antigens in bc patient ...201121498713
short communication: mouse mammary tumor virus driven α-lactalbumin expression effects on lactation and fertility of transgenic mice.α-lactalbumin (alac) is one of the major milk proteins. its gene expression is restricted to epithelial cells of the lactating mammary gland. the alac interaction with a uridine 5'-diphosphate-galactosyltransferase induces lactose synthesis, a major osmotic regulator of milk secretion. other functions attributed to this protein include induction of apoptosis and anti-inflammatory activities. to assess if forced expression of this gene during early gestation or involution could affect mammary phy ...201121524533
differentiation generates paracrine cell pairs that maintain basaloid mouse mammary tumors: proof of concept.there is a paradox offered up by the cancer stem cell hypothesis. how are the mixed populations that are characteristic of heterogeneous solid tumors maintained at constant proportion, given their high, and different, mitotic indices? in this study, we evaluate a well-characterized mouse model of human basaloid tumors (induced by the oncogene wnt1), which comprise mixed populations of mammary epithelial cells resembling their normal basal and luminal counterparts. we show that these cell types a ...201121541292
lactation defect in a widely used mmtv-cre transgenic line of mice.mmtv-cre mouse lines have played important roles in our understanding about the functions of numerous genes in mouse mammary epithelial cells during mammary gland development and tumorigenesis. however, numerous studies have not included mmtv-cre mice as controls, and many investigators have not indicated which of the different mmtv-cre founder lines were used in their studies. here, we describe a lactation defect that severely limits the use of one of the most commonly used mmtv-cre founder lin ...201121559430
breast cancer special feature: disruption of bone morphogenetic protein receptor 2 (bmpr2) in mammary tumors promotes metastases through cell autonomous and paracrine mediators.bone morphogenetic proteins (bmps) are members of the tgf-β superfamily of signaling molecules. bmps can elicit a wide range of effects in many cell types and have previously been shown to induce growth inhibition in carcinoma cells as well as normal epithelia. recently, it has been demonstrated that bmp4 and bmp7 are overexpressed in human breast cancers and may have tumor suppressive and promoting effects. we sought to determine whether disruption of the bmp receptor 2 (bmpr2) would alter mamm ...201121576484
the biological effects of antisense mos expression in fibroblasts.in order to determine the physiological significance of c-mos rna expression in somatic cells, we introduced antisense c-mos under the control of an inducible promoter. nih/3t3 cells were stably transfected with antisense mos under the control of the mouse mammary tumor virus long terminal repeat (mmtv-ltr). positive transfectants were selected under g418 conditions. following selection, nih/3t3 cells that received the antisense mos failed to form foci, whereas sense mos transfected cells grew n ...199721528318
structural status of the int loci in women showing high incidence of breast cancer.mammary carcinomas in certain mice strains are induced following infection by the mmtv. insertion of mmtv provirus into the int-1 and int-2 loci results in transcriptional activation of these two proto-oncogenes and is thought to be a key step in breast tumorigenesis in mice. a viral etiology for human breast cancers, though proposed several years ago, is far from proven. however, morphological structures resembling bittner's particles have been observed earlier in about 39% samples of breast tu ...199621541585
both dietary calorie and fat affect the growth of transplanted mammary-tumors in riii/sa mice - the effect of calorie is more profound than the effect of fat.the effects of dietary calories and/or fat on the growth of mammary tumor transplants, their expression of mouse mammary tumor virus (mmtv) and the incidence of lung metastasis were examined in riii/sa mice. starting at 3-4 weeks of age, groups of female mice were fed either high isocaloric diets (16 kcal/day/mouse) containing 25% or 5% corn or fish oil or low isocaloric (10 kcal/day/mouse) diets containing 25% or 5% fish or corn oil. after one week, small pieces (2x2x2 mm) of tumor tissue, prep ...199521556651
presence of the mouse mammary-tumor virus (mmtv) pol gene in breast-cancer.we have used the polymerase chain reaction (pcr) to detect sequences related to the mouse mammary tumor virus (mmtv) reverse transcriptase gene in dna from breast cancer cell lines and an extensive series of breast tumors. similar mmtv-related sequences were observed in dna from normal tissues. the segments amplified by pcr showed over 90% homology to the nucleotide sequence of the mmtv pol gene and no significant differences were noted between the dna from normal or tumor tissue. when the ampli ...199221584569
leptin deficiency suppresses mmtv-wnt-1 mammary tumor growth and abrogates tumor initiating cell survival.obesity increases both the risk and mortality associated with many types of cancer including that of the breast. in mice, obesity increases both incidence of spontaneous tumors and burden of transplanted tumors. our findings identify leptin, an adipose secreted cytokine, in promoting increased mammary tumor burden in obese mice and provide a link between this adipokine and cancer. using a transplantable tumor that develops spontaneously in the murine mammary tumor virus (mmtv)-wnt-1 transgenic m ...201121636700
tumor microenvironment-derived proteins dominate the plasma proteome response during breast cancer induction and progression.tumor development relies upon essential contributions from the tumor microenvironment and host immune alterations. these contributions may inform the plasma proteome in a manner that could be exploited for cancer diagnosis and prognosis. in this study, we employed a systems biology approach to characterize the plasma proteome response in the inducible her2/neu mouse model of breast cancer during tumor induction, progression, and regression. mass spectrometry data derived from approximately 1.6 m ...201121653680
notch-induced mammary tumorigenesis does not involve the lobule-limited epithelial progenitor.the mouse mammary epithelial cell hierarchy contains both multipotent stem cell as well as lineage-limited duct and lobular progenitor cell functions. the latter-also termed parity-identified mammary epithelial cells (pi-mecs)-are marked by beta-galactosidase (+¦ gal) expression following pregnancy and involution in whey acidic protein promoter (wap)-cre/rosa26-flox-stop-flox-lacz (wc/r26) mice, and are the targets of tumorigenic transformation in mouse mammary tumor virus-erbb2 transgenic mice. ...201121666720
methods to study dynamic interaction of androgen receptor with chromatin in living cells.androgen receptor (ar) is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily. in the presence of its specific ligands, ar translocates into the nucleus, interacts with chromatin at hormone response elements (hres) and recruits a variety of coregulators and basal transcription factors to regulate transcription. using green fluorescent protein (gfp) labelling and the tandem gene array system of mouse mammary tumour virus (mmtv), the interaction of ar with hres ...201121796525
nedd9 and bcar1 negatively regulate e-cadherin membrane localization, and promote e-cadherin degradation.the cas scaffolding proteins (nedd9/hef1/cas-l, bcar1/p130cas, efssin, and hepl/cass4) regulate cell migration, division and survival, and are often deregulated in cancer. high bcar1 expression is linked to poor prognosis in breast cancer patients, while upregulation of nedd9 contributes to the metastatic behavior of melanoma and glioblastoma cells. our recent work knocking out the single drosophila cas protein, dcas, identified a genetic interaction with e-cadherin. as e-cadherin is often downr ...201121765937
misexpression of wingless-related mmtv integration site 5a in mouse mammary gland inhibits the milk ejection response and regulates connexin43 phosphorylation.wingless-related mmtv integration site 5a (wnt5a) is a noncanonical signaling wnt that is expressed in all stages of mouse mammary gland development except lactation. using slow release pellets containing wnt5a, as well as wnt5a-null tissue, we previously showed that wnt5a acts to limit mammary development. here, we generated transgenic mice that overexpress wnt5a in the mammary epithelium using the mouse mammary tumor virus promoter (m5a mice). lactation was impaired in two high wnt5a expressin ...201121753195
[regulatory t cell depletion increases the number of cd8 cells during mouse mammary tumor virus infection.]mouse mammary tumor virus (mmtv) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. we have shown in a natural model of mmtv infection that the virus causes early and progressive increases in superantigen (sag)-specific cd4+ cd25+ foxp3+ regulatory t cells (treg) in peyer's patches. herein, we evaluated whether the depletion of treg cells affects the cd8+ population during milk-borne mmtv infection. at day 6 of infection, the depletion of ...201121745773
hierarchical cooperativity mediated by chromatin remodeling; the model of the mmtv transcription regulation.chromatin remodeling machineries are abundant and diverse in eukaryotic cells but their importance in gene expression remains unclear. although the influence of nucleosome position on the regulation of gene expression is generally envisioned under the equilibrium perspective, it is proposed that given the atp-dependence of chromatin remodeling enzymes, certain mechanisms necessitate non-equilibrium treatments. in particular, examination of the celebrated chromatin remodeling system of the mouse ...201121821052
leptin and cancer: from cancer stem cells to metastasis.there is growing evidence that obesity is a risk factor of cancer incidence and mortality. hence, the identification of the mechanistic links between obesity and cancer progression is emerging as a topic of widespread interest. recently, several groups have addressed the functional roles of leptin, an adipocyte-derived adipokine, for mammary tumor progression. in this issue of endocrine-related cancer, zheng et al. study the role of leptin on tumor growth in a xenograft model of mmtv-wnt1-derive ...201121680729
expression of truncated eukaryotic initiation factor 3e (eif3e) resulting from integration of mouse mammary tumor virus (mmtv) causes a shift from cap-dependent to cap-independent translation.integration of mouse mammary tumor virus (mmtv) at the common integration site int6 occurs in the gene encoding eif3e, the p48 subunit of translation initiation factor eif3. integration is at any of several introns of the eif3e gene and causes the expression of truncated eif3e mrnas. ectopic expression of the truncated eif3e protein resulting from integration at intron 5 (3e5) induces malignant transformation, but by an unknown mechanism. because eif3e makes up at least part of the binding site ...201121737453
dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism.the glucocorticoid receptor (gr), like other eukaryotic transcription factors, regulates gene expression by interacting with chromatinized dna response elements. photobleaching experiments in living cells indicate that receptors transiently interact with dna on the time scale of seconds and predict that the response elements may be sparsely occupied on average. here, we show that the binding of one receptor at the glucocorticoid response element (gre) does not reduce the steady-state binding of ...201121835447
abrogation of junctional adhesion molecule-a expression induces cell apoptosis and reduces breast cancer progression.intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. junctional adhesion molecule-a (jam-a) is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. in the present paper we show that jam-a acts as a survival factor for mammary carcinoma cells. jam-a null mice expressing polyoma middle t under mmtv promoter develop significantly smaller mammary tumors ...201121695058
In situ force mapping of mammary gland transformation.Tumor progression is characterized by an incremental stiffening of the tissue. The importance of tissue rigidity to cancer is appreciated, yet the contribution of specific tissue elements to tumor stiffening and their physiological significance remains unclear. We performed high-resolution atomic force microscopy indentation in live and snap-frozen fluorescently labeled mammary tissues to explore the origin of the tissue stiffening associated with mammary tumor development in PyMT mice. The tumo ...201121842067
Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary epithelial cells.Rspo2 was identified as a novel common integration site (CIS) for the mouse mammary tumor virus (MMTV) in viral induced mouse mammary tumors. Here we show that Rspo2 modulates Wnt signaling in mouse mammary epithelial cells. Co-expression of both genes resulted in an intermediate growth phenotype on plastic and had minor effects on the growth-promoting properties of Wnt1 in soft agar. However, individual Rspo2 and Wnt1 HC11 transfectants as well as the double transfectant were tumorigenic in ath ...201121732367
Chronic oral exposure to bisphenol A results in a nonmonotonic dose response in mammary carcinogenesis and metastasis in MMTV-erbB2 mice.Bisphenol A (BPA) is a synthetic compound used to produce plastics and epoxy resins. BPA can leach from these products in appreciable amounts, resulting in nearly ubiquitous daily exposure to humans. Whether BPA is harmful to humans, especially when administered orally in concentrations relevant to humans, is a topic of debate.201121988766
Alcohol Promotes Mammary Tumor Development via the Estrogen Pathway in Estrogen Receptor Alpha-Negative HER2/neu Mice.Background: Alcohol consumption is an established risk factor for breast cancer. Yet, the mechanism by which alcohol affects breast cancer development remains unresolved. The transition from the premenopausal to the postmenopausal phase is associated with a drastic reduction in systemic estrogen levels. It is not clear whether the risk of breast cancer attributable to alcohol consumption is modified by the different levels of estrogen found in pre- and postmenopausal women. The objective of thi ...201121981381
Development of Single-Vector Tet-on Inducible Systems with High Sensitivity to Doxycycline.Single-vector Tet-on systems were developed to enable the tight regulation of transgenes in mammalian cells with a low dosage of doxycycline. Both the regulatory and the responsive units were integrated in a single vector and separated by a short DNA segment (214 bp). In the developed single-vector Tet-on systems, a high level of expression of the transgene can be induced by doxycycline at a concentration of as low as 1 ng/ml, which is 500-1,000 times lower than that usually utilized in other Te ...201122002194
haploinsufficiency in the prometastasis kiss1 receptor gpr54 delays breast tumor initiation, progression, and lung metastasis.activation of kiss1 receptor (kiss1r or gpr54) by its ligands (kisspeptins) regulates a diverse function both in normal physiology and pathophysiology. in cancer, kiss1r has been implicated in tumor angiogenesis and metastasis, but a broader evaluation of kiss1r in tumorigenesis and tumor progression is yet to be conducted. in this study, we used mouse models of kiss1r gene knockout and mouse mammary tumor virus-polyoma virus middle t antigen (mmtv-pymt)-induced breast cancer to conduct such an ...201121852382
foxa1 and glucocorticoid receptor crosstalk via histone h4k16 acetylation at a hormone regulated enhancer.the forkhead transcription factor foxa1 participates in many gene regulatory events with steroid hormone receptors, one example being the integrated mouse mammary tumor virus (mmtv) promoter. its enhancer harbors several foxa1 binding sites. foxa1 promotes glucocorticoid receptor (gr)-dna binding and transcription. here we analyze the regulatory capacity of gr, foxa1 and hormone in quantitative terms when reconstituted with the mmtv enhancer in xenopus oocytes. by titrating each component we dem ...201222001115
CD49f and CD61 identify Her2/neu-induced mammary tumor-initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFß signaling.Human epidermal growth factor receptor 2 (HER2)/Neu is overexpressed in 20-30% of breast cancers and associated with aggressive phenotypes and poor prognosis. For deciphering the role of HER2/Neu in breast cancer, mouse mammary tumor virus (MMTV)-Her2/neu transgenic mice that develop mammary tumors resembling human HER2-subtype breast cancer have been established. Several recent studies have revealed that HER2/Neu is overexpressed in and regulates self renewal of breast tumor-initiating cells (T ...201121996747
characterization of a full-length endogenous beta-retrovirus, eqerv-beta1, in the genome of the horse (equus caballus).information on endogenous retroviruses fixed in the horse (equus caballus) genome is scarce. the recent availability of a draft sequence of the horse genome enables the detection of such integrated viruses by similarity search. using translated nucleotide fragments from gamma-, beta-, and delta-retroviral genera for initial searches, a full-length beta-retrovirus genome was retrieved from a horse chromosome 5 contig. the provirus, tentatively named eqerv-beta1 (for the first equine endogenous be ...201121994749
Gata-3 negatively regulates the tumor-initiating capacity of mammary luminal progenitor cells and targets the putative tumor suppressor caspase-14.The transcription factor Gata-3 is a definitive marker of luminal breast cancers and a key regulator of mammary morphogenesis. Here we have explored a role for Gata-3 in tumor initiation and the underlying cellular mechanisms using a mouse model of "luminal-like" cancer. Loss of a single Gata-3 allele markedly accelerated tumor progression in mice carrying the mouse mammary tumor virus promoter-driven polyomavirus middle T antigen (MMTV-PyMT mice), while overexpression of Gata-3 curtailed tumori ...201121930782
Requirements for mouse mammary tumor virus rem signal Peptide processing and function.Mouse mammary tumor virus (MMTV) encodes a Rev-like protein, Rem, which is involved in the nuclear export and expression of viral RNA. Previous data have shown that all Rev-like functions are localized to the 98-amino-acid signal peptide (SP) at the N terminus of MMTV Rem or envelope proteins. MMTV-SP uses endoplasmic reticulum-associated degradation (ERAD) for protein trafficking. Rem cleavage by signal peptidase in the ER is necessary for MMTV-SP function in a reporter assay, but many requirem ...201222072771
targeted expression of gli1 in the salivary glands results in an altered differentiation program and hyperplasia.hedgehog (hh) signaling is a regulator of salivary gland morphogenesis, but its role in postnatal glands has only recently begun to be addressed. to examine the effects of deregulated hh signaling in the salivary gland, we expressed the hh effector protein gli1, in salivary epithelial cells using both cytokeratin 5 and mouse mammary tumor virus (mmtv) transgenic systems. ectopic pathway activation resulted in restrained acinar differentiation, formation of cystic lesions, and prominent appearanc ...201121933656
microbiology. gut bacteria lend a molecular hand to viruses. 201121998362
a mouse mammary tumor virus env-like exogenous sequence is strictly related to progression of human sporadic breast carcinoma.a viral etiology of human breast cancer (hbc) has been postulated for decades since the identification of mouse mammary tumor virus (mmtv). the detection of mmtv env-like exogenous sequences (mmtvels) in 30% to 40% of invasive hbcs increased attention to this hypothesis. looking for mmtvels during cancer progression may contribute to a better understanding of their role in hbc. herein, we analyzed hbc preinvasive lesions for the presence of mmtvels. samples were obtained by laser microdissection ...201121854742
myb is essential for mammary tumorigenesis.myb oncogene upregulation is associated with estrogen receptor (er)-positive breast cancer, but disease requirements for myb function in vivo have not been explored. in this study, we provide evidence of a critical requirement for myb functions in models of human and murine breast cancer. in human breast cancer, we found that myb expression was critical for tumor cell growth both in vitro and in vivo in xenograft settings. in transgenic knockout mice, tissue-specific deletion of the murine myb g ...201121948968
impact of chromatin structure and dynamics on pr signaling. the initial steps in hormonal gene regulation.gene regulation requires access of transcription factors to dna sequences of target genes, which is limited by the compaction of dna in chromatin. based on our studies on the progesterone receptor (pr)-dependent hormonal induction of mouse mammary tumor virus (mmtv) promoter we found that remodeling of the various levels of chromatin organization is a complex and necessary prerequisite for regulation. two consecutive cycles are essential for transcriptional activation, both involving the collabo ...201121945605
successful transmission of a retrovirus depends on the commensal microbiota.to establish chronic infections, viruses must develop strategies to evade the host's immune responses. many retroviruses, including mouse mammary tumor virus (mmtv), are transmitted most efficiently through mucosal surfaces rich in microbiota. we found that mmtv, when ingested by newborn mice, stimulates a state of unresponsiveness toward viral antigens. this process required the intestinal microbiota, as antibiotic-treated mice or germ-free mice did not transmit infectious virus to their offspr ...201121998394
an update on primary hip osteoarthritis including altered wnt and tgf-β associated gene expression from the bony component of the disease.the study of primary hip oa is continuing to redefine what was once considered a stagnant pathology as one of dynamic change, occurring over a long period of time involving the many composite tissue types of the joint including the bone. examination of the inverse relationships evident between oa and fracture cohorts, including individuals with osteoporosis (op), indicates an imbalance in formation and resorption in the bony component of both pathologies. this review contains an overview of prim ...201121984764
combined treatment with exogenous estradiol and progesterone increases the incidence of breast cancer in ta2 mice without ovaries.ta2 mice have a high incidence of spontaneous breast cancer without chemical stimulus. there are two proposed explanations for this phenomenon: one is gravidity and the frequency of pregnancies, and the other is related to the presence of the mouse mammary tumor virus (mmtv). mmtv is hormonally regulated and indirectly promotes tumor formation by leading to the activation of wnt oncogenes through insertional mutagenesis. in order to clarify the relationship between estrogen, progesterone, mmtv, ...201121852035
mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor.fibroblast growth factor receptor 1 (fgfr1) is an oncoprotein with known involvement in mammary tumorigenesis. to understand how fgfr1 signaling promotes mammary tumorigenesis, an inducible fgfr1 (ifgfr1) system was created previously. previous studies have demonstrated that upon ifgfr1 activation in vivo, the epidermal growth factor (egf) ligands amphiregulin (areg) and epiregulin (ereg) are upregulated. both areg and ereg interact with the egf receptor (egfr). here, we investigated whether the ...201121868365
tumorigenesis related to retroviral infections.retroviral infections are considered important risk factors for cancer development in humans since approximately 15-20% of cancer worldwide is caused by an infectious agent. this report discusses the most established oncogenic retroviruses, including human immunodeficiency virus (hiv), human t-cell leukemia virus (htlv-1 and -2), rous sarcoma virus (rsv), abelson murine leukemia virus (a-mulv), moloney murine leukemia virus (m-mulv), murine mammary tumor virus (mmtv), bovine leukemia virus, (blv ...201122112727
Lysyl oxidase regulates MMTV promoter: indirect evidence of histone H1 involvement.Lysyl oxidase (LOX) is the enzyme that facilitates the cross-linking of collagen and elastin, although other functions for this enzyme have been indicated. Of these other functions, we describe herein the ability of LOX to regulate several gene promoters, like collagen III, elastin, and cyclin D1. We have previously demonstrated a specific binding between LOX and histone H1, in vitro. Therefore, we investigated whether LOX would affect the mouse mammary tumor virus (MMTV) promoter and its glucoc ...201121999391
airway response to acute mechanical stress in a human bronchial model of stretch.abstract: introduction: lung inflation may have deleterious effects on the alveoli during mechanical ventilation. however, the consequences of stretch during excessive lung inflation on basal tone and responsiveness of human bronchi are unknown. this study was undertaken to devise an experimental model of acute mechanical stretch in isolated human bronchi and to investigate its effect on airway tone and responsiveness. methods: bronchi were removed from 48 thoracic surgery patients. after prepa ...201121914176
Mouse mammary tumor virus in human breast cancer red herring or smoking gun? 201121884676
The 5' Leader Sequence of Mouse Mammary Tumor Virus Enhances Expression of the Envelope and Reporter Genes.Mouse mammary tumor virus (MMTV) is a complex betaretrovirus, which utilizes a Rev-like auxiliary protein Rem to export the unspliced viral RNA from the nucleus. MMTV env mRNA appears to be exported via a distinct, Rem-independent, mechanism. Here, we analyzed the effect of an extensively folded region coinciding with the 5' leader sequence on env gene expression. We found that the presence of the 5' leader stimulates expression of the envelope protein. Enhanced Env production was accompanied b ...201122113011
mouse mammary tumor virus-like gene sequences are present in lung patient specimens.previous studies have reported on the presence of murine mammary tumor virus (mmtv)-like gene sequences in human cancer tissue specimens. here, we search for mmtv-like gene sequences in lung diseases including carcinomas specimens from a mexican population. this study was based on our previous study reporting that the iner51 lung cancer cell line, from a pleural effusion of a mexican patient, contains mmtv-like env gene sequences.201121943279
High-throughput semiquantitative analysis of insertional mutations in heterogeneous tumors.Retroviral and transposon-based insertional mutagenesis (IM) screens are widely used for cancer gene discovery in mice. Exploiting the full potential of IM screens requires methods for high-throughput sequencing and mapping of transposon and retroviral insertion sites. Current protocols are based on ligation-mediated PCR amplification of junction fragments from restriction endonuclease-digested genomic DNA, resulting in amplification biases due to uneven genomic distribution of restriction enzym ...201121852388
investigation of human jc and bk polyomaviruses in breast carcinomas.we have previously showed the presence of the simian virus 40 (sv40) and the mouse mammary tumor virus (mmtv)-like in a significant proportions of tunisian breast carcinomas. however, to date there are no published studies concerning evaluation of the possible implication of the human polyomaviruses jc (jcv) and bk (bkv) in breast carcinomas. the presence of jcv and bkv dna was investigated by pcr in a 123 primary breast carcinomas and matched adjacent non-tumor breast tissues. the results were ...201122108781
Assaying chromatin structure and remodeling by restriction enzyme accessibility.The packaging of eukaryotic DNA into nucleosomes, the fundamental unit of chromatin, creates a barrier to nuclear processes, such as transcription, DNA replication, recombination, and repair. This obstructive nature of chromatin can be overcome by the enzymatic activity of chromatin remodeling complexes, which create a more favorable environment for the association of essential factors and regulators to sequences within target genes. Here, we describe a detailed approach for analyzing chromatin ...201222183589
novel common integration sites targeted by mouse mammary tumor virus insertion in mammary tumors have oncogenic activity.non-acute transforming retroviruses like mouse mammary tumor virus (mmtv) cause cancer, at least in part, through integration near cellular genes involved in growth control, thereby de-regulating their expression. it is well-established that mmtv commonly integrates near and activates expression of members of the wnt and fgf pathways in mammary tumors. however, there are a significant number of tumors for which the proviral integration sites have not been identified. here, we used high through-p ...201122087314
lack of association of mouse mammary tumor virus-like sequences in iranian breast cancer patients.objective: the present study aimed to detect mouse mammary tumor virus (mmtv)-like sequences in iranian breast cancer patients in the city of shiraz, located in southwest iran. subjects and methods: we searched for two mmtv genetic regions in the peripheral blood leukocytes of 300 women with breast cancer, 300 age-matched healthy control subjects, and 50 breast tumor tissues. two regions of mmtv, 660 bp and 250 bp, were searched by nested polymerase chain reactions. results: none of the above tw ...201122213781
apc mutation enhances pymt-induced mammary tumorigenesis.the adenomatous polyposis coli (apc) tumor suppressor gene is silenced by hypermethylation or mutated in up to 70% of human breast cancers. in mouse models, apc mutation disrupts normal mammary development and predisposes to mammary tumor formation; however, the cooperation between apc and other mutations in breast tumorigenesis has not been studied. to test the hypothesis that loss of one copy of apc promotes oncogene-mediated mammary tumorigenesis, apc(min/+) mice were crossed with the mouse m ...201122216254
trisomy chromosome 5 is a recurrent cytogenetic lesion in mammary tumors from parous mmtv-erbb-2 transgenic mice.erbb-2 is amplified or overexpressed in approximately 30% of human breast cancers, and has been associated with poor prognosis and therapeutic resistance. previous studies have suggested that erbb-2 overexpression in transgenic mice induces genomic instability; however, the patterns of genetic lesions vary with individual model systems. the development of mammary tumors in multiparous murine mammary tumor virus (mmtv)-erbb-2 transgenic mice is accelerated due to hormonal interactions which induc ...201122848270
loss of the 14-3-3σ tumor suppressor is a critical event in erbb2-mediated tumor progression.14-3-3σ is a putative tumor suppressor involved in cell-cycle progression and epithelial polarity. we demonstrate that loss of one or both copies of the conditional 14-3-3σ allele results in accelerated mammary and salivary tumorigenesis in mice expressing an activated erbb2 oncogene under the endogenous erbb2 promoter. significantly, the majority of tumors bearing a single conditional 14-3-3σ allele lose expression of the remaining 14-3-3σ allele, which is associated with epigenetic methylation ...201122585169
effects of pb190 and pb212, new σ receptor ligands, on glucocorticoid receptor-mediated gene transcription in lmcat cells.the hyperactivity of the hypothalamic-pituitary-adrenocortical (hpa) axis is often observed in patients with major depression. it has even been implicated in the pathophysiology of this disease. some antidepressant drugs (ads) inhibit glucocorticoid receptor (gr) function under in vitro conditions. the σ(1) receptor agonists reveal potential antidepressant activity in animals, moreover, igmesine is promising as an ad in humans. as already shown, σ receptors are involved in stress-induced respons ...201122358106
effects of soy isoflavone and endogenous oestrogen on breast cancer in mmtv-erbb2 transgenic mice.soy isoflavone is associated with modification of breast cancer risk. effects of dietary isoflavone on breast tissue carcinogenesis under varying endogenous oestrogen contexts were investigated.201223321163
with a little help from my enteric microbial friends.although the disciplines of bacteriology and virology frequently come together in the setting of a diagnostic medical microbiology laboratory, the two scientific fields are usually miles apart. the microbiologists basically form two non-overlapping groups of scientists, the bacteriologists and virologists, which go to separate meetings and do not easily intermingle. some recent research findings about elegant virus-bacterium interactions may change this situation. obviously, interactions between ...201526029695
betaretroviral envelope subunits are noncovalently associated and restricted to the mammalian class.the structure of the transmembrane subunit (tm) of the retroviral envelope glycoprotein (env) is highly conserved among most retrovirus genera and includes a pair of cysteines that forms an intramolecular disulfide loop within the ectodomain. alpha-, gamma-, and deltaretroviruses have a third cysteine, adjacent to the loop, which forms a disulfide bond between tm and the surface subunit (su) of env, while lentiviruses, which have noncovalently associated subunits, lack this third cysteine. the b ...201223221553
glucocorticoid-mediated period2 induction delays the phase of circadian rhythm.glucocorticoid (gc) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including period1 (per1) and period2 (per2). however, no gc response element (gre) has been reported in the per2 promoter region. here we report the molecular mechanisms of per2 induction by gc signaling and its relevance to the regulation of circadian timing. we found that gc prominently induced per2 expression and delayed the circadian phase. the overlap ...201323620290
metabolic alterations in mammary cancer prevention by withaferin a in a clinically relevant mouse model.efficacy of withaferin a (wa), an ayurvedic medicine constituent, for prevention of mammary cancer and its associated mechanisms were investigated using mouse mammary tumor virus-neu (mmtv-neu) transgenic model.201323821767
convergent capture of retroviral superantigens by mammalian herpesviruses.horizontal gene transfer from retroviruses to mammals is well documented and extensive, but is rare between unrelated viruses with distinct genome types. three herpesviruses encode a gene with similarity to a retroviral superantigen gene (sag) of the unrelated mouse mammary tumour virus (mmtv). we uncover ancient retroviral sags in over 20 mammals to reconstruct their shared history with herpesviral sags, revealing that the acquisition is a convergent evolutionary event. a retrovirus circulating ...201526400439
viruses and breast cancer.viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. for over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. despite these efforts, the establishment of conclusive evidence for such a role has been elusive. however, the development of extremely sophisticated new experimenta ...201024281093
comparison of prostate-specific promoters and the use of psp-driven virotherapy for prostate cancer.prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men today. although virus-based gene therapy is a promising strategy to combat advanced prostate cancer, its current effectiveness is limited partially due to inefficient cellular transduction in vivo. to overcome this obstacle, conditional oncolytic viruses (such as conditional replication adenovirus (crad)) are developed to specifically target prostate without (or with minimal) systemic tox ...201323484134
targeting deoxyhypusine hydroxylase activity impairs cap-independent translation initiation driven by the 5'untranslated region of the hiv-1, htlv-1, and mmtv mrnas.replication of the human immunodeficiency virus type 1 (hiv-1) is dependent on eif5a hypusination. hypusine is formed post-translationally on the eif5a precursor by two consecutive enzymatic steps; a reversible reaction involving the enzyme deoxyhypusine synthase (dhs) and an irreversible step involving the enzyme deoxyhypusine hydroxylase (dohh). in this study we explored the effect of inhibiting dohh activity and therefore eif5a hypusination, on hiv-1 gene expression. results show that the exp ...201627633452
one-step separation of myristoylated and nonmyristoylated retroviral matrix proteins.n-terminal myristoylation of retroviral matrix proteins is essential for the targeting of the gag polyproteins to the plasma membrane. to investigate the effect of the myristoylation on the structure and membrane binding ability of the matrix proteins, it is necessary to prepare their myristoylated forms. we present purification of myristoylated matrix proteins of the mouse mammary tumor virus and murine leukemia virus, two morphogenetically distinct retroviruses. the proteins were expressed in ...201324056256
oncogenic wnt3a expression as an estimable prognostic marker for hepatocellular carcinoma.to investigate member 3a of wingless-type mmtv integration site family (wnt3a) expression in cancerous and surrounding tissues and the relationship between clinicopathologic features of hepatocellular carcinoma (hcc) and wnt3a expression.201627076768
abnormality of wnt3a expression as novel specific biomarker for diagnosis and differentiation of hepatocellular carcinoma.the member 3a of wingless-type mmtv integration site family (wnt3a) as an oncogene is overexpressed in many kinds of tumors with a worse outcome. however, the mechanism and alteration of wnt3a expression in hepatocellular carcinoma (hcc) have not been clarified. in this study, the levels of wnt3a expression were investigated in 80 hcc tissues or sera of 186 patients with chronic liver diseases. the incidence of hepatic wnt3a expression in hcc tissues was 96.25 % and significantly higher (χ (2) = ...201626577850
hepatic interferon-stimulated genes are differentially regulated in the liver of chronic hepatitis c patients with different interleukin-28b genotypes.pretreatment up-regulation of hepatic interferon (ifn)-stimulated genes (isgs) has a stronger association with the treatment-resistant interleukin (il)28b minor genotype (mi; tg/gg at rs8099917) than with the treatment-sensitive il28b major genotype (ma; tt at rs8099917). we compared the expression of isgs in the liver and blood of 146 patients with chronic hepatitis c who received pegylated ifn and ribavirin combination therapy. gene expression profiles in the liver and blood of 85 patients wer ...201424311440
role of novel retroviruses in chronic liver disease: assessing the link of human betaretrovirus with primary biliary cirrhosis.a human betaretrovirus resembling mouse mammary tumor virus has been characterized in patients with primary biliary cirrhosis. the agent triggers a disease-specific phenotype in vitro with aberrant cell-surface expression of mitochondrial antigens. the presentation of a usually sequestered self-protein is thought to lead to the loss of tolerance and the production of anti-mitochondrial antibodies associated with the disease. similar observations have been made in mouse models, where mouse mammar ...201525754451
is there a role for cyclophilin inhibitors in the management of primary biliary cirrhosis?autoimmune hepatitis (aih) and primary biliary cirrhosis (pbc) are poorly understood autoimmune liver diseases. immunosuppression is used to treat aih and ursodeoxycholic acid is used to slow the progression of pbc. nevertheless, a proportion of patients with both disorders progress to liver failure. following liver transplantation, up to a third of patients with pbc experience recurrent disease. moreover a syndrome referred to as "de novo aih" occurs in a proportion of patients regardless of ma ...201323348060
[viral superantigens].superantigens (sags) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of t cells via an unconventional mechanism. they cause polyclonal activation of t cells in a non-specific manner, by binding to a particular variable-beta (vβ) chain of t-cell receptor (tcr) and mhc class ii molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the t cell. sags are classified into three ...201627525406
oncogenic effects of wnt5a in epstein-barr virus‑associated nasopharyngeal carcinoma.the molecular events that drive the progression of epstein-barr virus (ebv)-associated nasopharyngeal carcinoma (npc) are still to be elucidated. here, we report for the first time the pathogenic significance of an npc-associated gene, wingless-type mmtv integration site family, member 5a (wnt5a) and the contribution of ebv to its expression. wnt5a is a representative wnt protein that activates non-canonical wnt signalling. with regard to its role in carcinogenesis, there is conflicting evidence ...201424626628
no association between epstein-barr virus and mouse mammary tumor virus with breast cancer in mexican women.breast cancer is the most frequent malignancy affecting women worldwide. it has been suggested that infection by epstein barr virus (ebv), mouse mammary tumor virus or a similar virus, mmtv-like virus (mmtv-lv), play a role in the etiology of the disease. however, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. here, we used polymerase chain reaction assay to screen specific sequences of ebv ...201324131889
carcinogenic viruses and solid cancers without sufficient evidence of causal association.viral infections are important risk factors for tumor development in humans. selected types of cancers, either lymphomas or carcinomas, for which there is sufficient evidence in humans of a causal association with specific viruses, have been identified. experimental and clinical data on the possible association of other tumor types and carcinogenic viruses are presently controversial. in this article, we review the current evidence on the relationship between breast, colorectal and lung cancers ...201323280523
epstein-barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.the purpose of this investigation is to determine if epstein barr virus (ebv), high risk human papillomavirus (hpv), and mouse mammary tumour viruses (mmtv) co-exist in some breast cancers.201223183846
are viruses associated with human breast cancer? scrutinizing the molecular evidence.the three viruses most studied as possible causes of human breast cancer are mouse mammary tumor virus-like sequences (mmtv-ls), epstein-barr virus (ebv), and oncogenic (high risk) types of human papilloma virus (hpv). the first step in fulfilling traditional criteria for inferring that a cancer is caused by a virus is to demonstrate the virus in the affected tissue. molecular techniques, compared to host antibody assessment and immunohistochemistry, are the most definitive in establishing viral ...201222274134
mouse mammary tumor virus signal peptide uses a novel p97-dependent and derlin-independent retrotranslocation mechanism to escape proteasomal degradation.multiple pathogens, including viruses and bacteria, manipulate endoplasmic reticulum-associated degradation (erad) to avoid the host immune response and promote their replication. the betaretrovirus mouse mammary tumor virus (mmtv) encodes rem, which is a precursor protein that is cleaved into a 98-amino-acid signal peptide (sp) and a c-terminal protein (rem-ct). sp uses retrotranslocation for er membrane extraction and yet avoids erad by an unknown mechanism to enter the nucleus and function as ...201728351922
the conformational feasibility for the formation of reaching dimer in asv and hiv integrase: a molecular dynamics study.retroviral integrases are reported to form alternate dimer assemblies like the core-core dimer and reaching dimer. the core-core dimer is stabilized predominantly by an extensive interface between two catalytic core domains. the reaching dimer is stabilized by n-terminal domains that reach to form intermolecular interfaces with the other subunit's core and c-terminal domains (ctd), as well as ctd-ctd interactions. in this study, molecular dynamics (md), brownian dynamics (bd) simulations, and fr ...201627835934
effects of modification of the hiv-1 env cytoplasmic tail on immunogenicity of vlp vaccines.we investigated the effects on assembly and antigenic properties of specific modifications of the transmembrane spanning (tms) and cytoplasmic tail (ct) domains of hiv-1 env from a transmitted/founder (t/f) zm53 env glycoprotein. a construct containing a short version of the tms domain derived from the mouse mammary tumor virus (mmtv) env with or without a gcn4 trimerization sequence in the ct exhibited the highest levels of incorporation into vlps and induced the highest titers of anti-env igg ...201626761396
myristoylation drives dimerization of matrix protein from mouse mammary tumor virus.myristoylation of the matrix (ma) domain mediates the transport and binding of gag polyproteins to the plasma membrane (pm) and is required for the assembly of most retroviruses. in betaretroviruses, which assemble immature particles in the cytoplasm, myristoylation is dispensable for assembly but is crucial for particle transport to the pm. oligomerization of hiv-1 ma stimulates the transition of the myristoyl group from a sequestered to an exposed conformation, which is more accessible for mem ...201626728401
mouse mammary tumor virus-based vector transduces non-dividing cells, enters the nucleus via a tnpo3-independent pathway and integrates in a less biased fashion than other retroviruses.mouse mammary tumor virus (mmtv) is a complex, milk-born betaretrovirus, which preferentially infects dendritic cells (dc) in the gastrointestinal tract and then spreads to t and b lymphocytes and finally to the mammary gland. it is not clear how the prototypic betaretrovirus infects mucosal dcs and naïve lymphocytes as these cells are considered to be non-proliferative. studies of mmtv biology have been hampered by the difficulty of obtaining sufficient virus/vector titers after transfection of ...201424779422
revisiting a role for a mammary tumor retrovirus in human breast cancer.there remains great controversy as to whether mouse mammary tumor virus (mmtv), the etiological agent of mammary cancer in mice, or a closely related human retrovirus, plays a role in the development of breast cancer in humans. on one hand, retroviruses such as human t-cell lymphotropic virus and human immunodeficiency virus (hiv) are known causative agents of cancer (in the case of hiv, albeit, indirectly), but attempts to associate other retroviruses with human cancers have been difficult. a r ...201323580334
apobec3 inhibition of mouse mammary tumor virus infection: the role of cytidine deamination versus inhibition of reverse transcription.the apolipoprotein b editing complex 3 (apobec3) family of proteins is a group of intrinsic antiviral factors active against a number of retroviral pathogens, including hiv in humans and mouse mammary tumor virus (mmtv) in mice. apobec3 restricts its viral targets through cytidine deamination of viral dna during reverse transcription or via deaminase-independent means. here, we used virions from the mammary tissue of mmtv-infected inbred wild-type mice with different allelic apobec3 variants (ap ...201323449789
sequences within both the 5' utr and gag are required for optimal in vivo packaging and propagation of mouse mammary tumor virus (mmtv) genomic rna.this study mapped regions of genomic rna (grna) important for packaging and propagation of mouse mammary tumor virus (mmtv). mmtv is a type b betaretrovirus which preassembles intracellularly, a phenomenon distinct from retroviruses that assemble the progeny virion at cell surface just before budding such as the type c human and feline immunodeficiency viruses (hiv and fiv). studies of fiv and mason-pfizer monkey virus (mpmv), a type d betaretrovirus with similar intracellular virion assembly pr ...201223077548
ifn-α and lipopolysaccharide upregulate apobec3 mrna through different signaling pathways.apobec3 (a3) proteins are virus-restriction factors that provide intrinsic immunity against infections by viruses like hiv-1 and mouse mammary tumor virus. a3 proteins are inducible by inflammatory stimuli, such as lps and ifn-α, via mechanisms that are not fully defined. using genetic and pharmacological studies on c57bl/6 mice and cells, we show that ifn-α and lps induce a3 via different pathways, independently of each other. ifn-α positively regulates mouse apobec3 (ma3) mrna expression throu ...201222972924
a novel role for apobec3: susceptibility to sexual transmission of murine acquired immunodeficiency virus (maids) is aggravated in apobec3 deficient mice.apobec3 proteins are host factors that restrict infection by retroviruses like hiv, mmtv, and mlv and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. previously, we showed that apobec3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. in this present study, we used apobec3 knockout mice and their wild type counterpart to query the ...201222691411
bone marrow stromal cell antigen 2 (bst-2) restricts mouse mammary tumor virus (mmtv) replication in vivo.bone marrow stromal cell antigen 2 (bst-2) is a cellular factor that restricts the egress of viruses such as human immunodeficiency virus (hiv-1) from the surface of infected cells, preventing infection of new cells. bst-2 is variably expressed in most cell types, and its expression is enhanced by cytokines such as type i interferon alpha (ifn-α). in this present study, we used the beta-retrovirus, mouse mammary tumor virus (mmtv) as a model to examine the role of mouse bst-2 in host infection i ...201222284121
translation of mmtv gag requires nuclear events involving splicing motifs in addition to the viral rem protein and rmre.retroviral gag proteins are encoded in introns and, because of this localization, they are subject to the default pathways of pre-mrna splicing. retroviruses regulate splicing and translation through a variety of intertwined mechanisms, including 5'- post-transcriptional control elements, 3'- constitutive transport elements, and viral protein rna interactions that couple unspliced and singly spliced mrnas to transport machinery. sequences within the gag gene termed inhibitory or instability sequ ...201222277305
csf1r inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by cd8(+) t cells.increased numbers of tumor-infiltrating macrophages correlate with poor disease outcome in patients affected by several types of cancer, including breast and prostate carcinomas. the colony stimulating factor 1 receptor (csf1r) signaling pathway drives the recruitment of tumor-associated macrophages (tams) to the neoplastic microenvironment and promotes the differentiation of tams toward a pro-tumorigenic phenotype. twelve clinical trials are currently evaluating agents that target the csf1/csf1 ...201324498562
retroviral integrase protein and intasome nucleoprotein complex structures.retroviral replication proceeds through the integration of a dna copy of the viral rna genome into the host cellular genome, a process that is mediated by the viral integrase (in) protein. in catalyzes two distinct chemical reactions: 3'-processing, whereby the viral dna is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral dna ends are inserted into host chromosomal dna. although in has been studied as a recombinant protein since the 1980s, deta ...201728289517
biochemical characterization of novel retroviral integrase proteins.integrase is an essential retroviral enzyme, catalyzing the stable integration of reverse transcribed dna into cellular dna. several aspects of the integration mechanism, including the length of host dna sequence duplication flanking the integrated provirus, which can be from 4 to 6 bp, and the nucleotide preferences at the site of integration, are thought to cluster among the different retroviral genera. to date only the spumavirus prototype foamy virus integrase has provided diffractable cryst ...201324124581
lack of evidence for human t-lymphotropic virus type 1 and mouse mammary tumor-like virus involvement in the genesis of childhood acute lymphoblastic leukemia.in mexico city, the incidence of childhood acute lymphoblastic leukemia (all) is one of the highest in the world; epidemiologic evidence suggests that infectious agents could be involved in the genesis of this disease. early transmitted oncogenic retroviruses infecting lymphocytes are important candidates.201324019395
the human endogenous retrovirus k(hml-2) has a broad envelope-mediated cellular tropism and is prone to inhibition at a post-entry, pre-integration step.the herv-k(hml-2) family is the most recent addition to the collection of human endogenous retroviruses. it comprises proviruses that encode functional proteins that can assemble into replication defective particles carrying the envelope protein. using a reconstituted herv-k113 envelope sequence, we have analyzed its ability to mediate entry into a set of 33 cell lines from 10 species. of these, 30 were permissive, demonstrating an amphotropism consistent with a broad expression of receptor prot ...201626517399
endogenous mouse mammary tumor viruses (mtv): new roles for an old virus in cancer, infection, and immunity.mouse mammary tumor viruses are beta-retroviruses that exist in both exogenous (mmtv) and endogenous (mtv) forms. exogenous mmtv is transmitted via the milk of lactating animals and is capable of inducing mammary gland tumors later in life. mmtv has provided a number of critical models for studying both viral infection as well as human breast cancer. in addition to the horizontally transmitted mmtv, most inbred mouse strains contain permanently integrated mtv proviruses within their genome that ...201324324930
epidemiological and phylogenetic analysis of institutional mouse parvoviruses.mouse parvoviruses (mpvs) are small, single-stranded, 5 kb dna viruses that are subclinical and endemic in many laboratory mouse colonies. mpvs cause more distinctive deleterious effects in immune-compromised or genetically-engineered mice than immuno-competent mice. at the university of louisville (u of l), there was an unexpected increase of mpv sero-positivity for mpv infections in mouse colonies between january 2006 and february 2007, resulting in strategic husbandry changes aimed at control ...201323545399
virions at the gates: receptors and the host-virus arms race.all viruses need to bind to specific receptor molecules on the surface of target cells to initiate infection. virus-receptor binding is highly specific, and this specificity determines both the species and the cell type that can be infected by a given virus. in some well-studied cases, the virus-binding region on the receptor has been found to be unrelated to the receptor's normal cellular function. resistance to virus infection can thus evolve by selection of mutations that alter amino acids in ...201323723739
erratum to: mouse mammary tumor-like virus (mmtv) is present in human breast tissue before development of virally associated breast cancer.[this corrects the article doi: 10.1186/s13027-016-0113-6.].201728316641
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