Strain C3H-A
            <sup>vy</sup>
            fB Mice: Ninety Percent Incidence of Mammary Tumors Transmitted by Either Parent

Vlahakis, George; Heston, W. E.; Smith, Gilbert H.

doi:10.1126/science.170.3954.185

Cited by 27 publications

(14 citation statements)

References 6 publications

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“…hybrids would have a diminished mammary tumor incidence since both genes would be present although heterozygous. We observed approximately a 67 % mammary tumor reduction in (A"YA)F1 females (28.9 %/90 %) compared to that expected when both A' Y and Mtv-1 are present (Vlahakis et al, 1970). A further reduction in mammary tumor incidence was observed in the BC females.…”

Section: Discussioncontrasting

confidence: 33%

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐a^vyfb × c3h/sm mice

Smith

Henry

Vlahakis

et al. 1982

Intl Journal of Cancer

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Mouse mammary tumor virus (MMTV)-specific RNA and antigen content of normal and neoplastic mouse mammary tissue were measured in strains C3HISm and C3H-A"VB, in C3H-A"fBO X C3HISmdF, hybrids and in (C3H-A"WB X C3HISm) X C3H/Smi3 backcross segrewts. Good correlation between M M N antigen expression in lactating mammary glands and mammary tumor incidence was observed in the parental mouse strains. The high-mammary-cancer strain C3H-Av7fB (90 %) had consistently high levels of M M N antigen in the mammary glands and tumors, whereas mammary tissues from lowmammary-cancer subline C3HISm (1.6 %), whether normal or neoplastic, had little or no detectable MMTV antigen. In contrast, MMTV RNA content of normal C3HISm mammary tissue was consistently as high as or higher than corresponding levels in C3H-A"yfB females. These molecular data, along with the relative mammary tumor incidences, suggest that the endogenous MMTV provirus expression gene Mtv-l present in C3H mice is fully expressed in the C3H-A"VB subline but is silent or more probably absent in the C3H/Sm subline. Our earlier genetic crosses between C3H-A"yfB and C3H/Sm mice were conducted to determine the effect of the AvY gene on mammary tumorigenesis during its segregation in backcross (BC) females produced from matings of the F, hybrid females with C3HISm males. Our mammary tumor incidence data presented in the accompanying paper strongly suggested the possibility that C3H/Sm mice possessed a dominant genetic factor(s) which specifically attenuated the tumorigenic effects of the A " y and M&-/ genes on the mammary gland without affecting the A' Y gene's enhancement of liver tumorigenesis and obesity.Examination of MMTV RNA and antigen content in (C3H-AVfB X C3H/Sm) hybrid and BC females showed that the expression of MMTV antigen was completely suppressed in the agouti (AA) BC females. However, yellow F, (A'YA) and yellow (A"YA) BC females continued to express MMTV antigen in their mammary glands even though mammary tumor incidence was significantly depressed.MMTV RNA levels were similar in all F, and BC females regardless of the presence or absence of the A"Y gene.Mammary tumor incidence was reduced in all the BC females (whose genome is 3/4 derived from C3HISm) relative to the F, females (whose genome is only 112 derived from C3H/Sm) suggesting that more than one gene is involved in the suppression of spontaneous mammary tumor development. Cessation of translational expression of endogenous MMTV occurred only in the agouti (An) BC females, suggesting an association between this phenomenon and the agouti locus of C3HISm. Evaluation of the relative M M N RNA content of nucleic and cytoplasmic fractions from C3HISm mammary tissues strongly suggests that transport andlor processing of MMTV RNA is defective in these mice. This defect probably accounts for the absence of detectable M M N antigens in C3HISm and agouti (AA ) BC mammary tissues and tumors and may contribute to the observed reduction in mammary tumor incidence.Various genes specifying resistance to andlo...

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Section: Discussioncontrasting

confidence: 33%

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐a^vyfb × c3h/sm mice

Smith

Henry

Vlahakis

et al. 1982

Intl Journal of Cancer

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“…Each high incidence mouse strain congenitally transmits highly infectious MMTV through the milk to their o spring. In addition, the C3H (Michalides et al, 1981, Smith and Vlahakis, 1982, van Nie and Verstraeten, 1975, Vlahakis et al, 1970 and GR (Michalides et al, 1985, van Nie et al, 1977 mouse strains each contain a dominantly-expressed, genetically transmitted or endogenous MMTV proviral genome (Mtv-1 and Mtv-2, respectively) that encodes an infectious virus that is also present in the milk. Parous C3H females develop pregnancy independent mammary tumors that frequently arise as clonal outgrowths from preneoplastic hyperplastic alveolar nodules (HAN) at 7 ± 10 months of age (Squartini, 1961).…”

Section: Inbred Mouse Strains Having a High Incidence Of Mammary Tumorsmentioning

confidence: 99%

“…Similarly, C3H mice in which the horizontally transmitted MMTV has been removed also develop pregnancy independent mammary tumors as a consequence of infection by the Mtv-1 encoded virus. These Mtv-1-induced tumors mainly arise in the second year of life (Smith and Vlahakis, 1982, van Nie and Verstraeten, 1975, Vlahakis et al, 1970. The GR, BR6 and RIII females have a high incidence of pregnancy dependent mammary tumors or plaques that, after one or more parities, progress to a pregnancy independent tumor (Lee, 1968, Squartini, 1961, Van Nie et al, 1977.…”

Section: Inbred Mouse Strains Having a High Incidence Of Mammary Tumorsmentioning

confidence: 99%

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

2000

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The study of the mouse mammary tumor virus (MMTV) has provided important insights into the mechanisms of gene transcription regulation by steroid hormones, the mode of action of heritable super antigens and the progressive nature of neoplastic transformation in the mammary gland. Here we describe the current situation with respect to the latter aspect of MMTV biology and the prospects for further advance in our understanding of breast cancer in humans that may be expected from a continued study of MMTV-induced mammary neoplasia. MMTV is a heritable somatic mutagen whose target range is limited. Commonly, the tumorigenic capacity of MMTV is restricted to mammary gland, whereas infection is found in a variety of cell types. In order to replicate, proviral DNA must be inserted into the cell DNA and cell division is required to ®x the mutation. Yet only in the mammary epithelium does this lead to neoplastic transformation. This suggests a unique relationship between MMTV and mammary epithelium. In evaluating this relationship, we and others have discovered genes and potential gene pathways that are pertinent in mammary di erentiation and neoplasia. In addition, the clonal nature of these progressive events from normal to malignant phenotype has become increasingly clear. The weight of these observations compel us to conclude that mammary neoplasms arise from multipotent mammary epithelial cells through a process of acquired mutations that are re¯ected in the increasingly malignant nature of the population of progeny produced by these damaged stem cells.

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“…Thirdly, in mice, traces of MMTV are detected in normal mouse breast tissues and epithelia: to date this has not been shown to be the case in human breast cancers for the MMTV-like virus [70]. Fourthly, pregnancy is protective against the risk of developing breast cancer in humans [12] and this is inconsistent with the murine MMTV model [30]. Nevertheless, the weight of early evidence of a serological link between breast cancer and reactivity to MMTV antigens, and the more recent evidence of an MMTV-like virus in breast cancers, together indicate that further investigations are justified.…”

Section: Discussionmentioning

confidence: 87%

“…However, inbred strains of mice (e.g. C3H) that contain dominantly expressed integrated MMTV genomes (provirus) can also transmit replicationcompetent virus from one generation to another [30][31][32][33][34]. In strains of mice derived from feral animals, devoid of integrated MMTV (such as Czech II mice), viral infections are transmitted solely by the milk of an infected mother and are not usually transmitted horizontally between adult mice [35,36].…”

Section: Viruses In the Aetiology Of Human Cancersmentioning

confidence: 99%

A Viral Aetiology for Breast Cancer: Time to Re-Examine the Postulate

Mant

Hodgson²,

Hobday

et al. 2004

Intervirology

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Despite decades of research, no aetiologic factor(s) for human breast cancer has been identified and the search for a causal agent has all but been abandoned during the past thirty years. Over 60 years ago, it was demonstrated that breast tumours in mice are caused by an oncornavirus, murine mammary tumour virus (MMTV). Whilst many at that time postulated a similar virus might be the causative agent of human breast cancer, genetic evidence was difficult to obtain primarily because of the occurrence of endogenous human retrovirus (HER) sequences within the human genome that share extensive regions of nucleotide homology with MMTV. Recently, there has been a resurgence of interest in the possibility that a significant proportion of human breast cancers may be caused by viral infections. Two candidate viruses have been proposed, a human retroviral analogue of MMTV (which differs significantly in sequence and characteristics from HERs) and, the Epstein-Barr virus (γ-herpes virus). These two viruses have been reported to occur in up to 37 and 50% of breast cancer cases, respectively. Here we present the background to the infectious hypothesis for the aetiology of breast cancer and review recent findings.

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Strain C3H-A ^vy fB Mice: Ninety Percent Incidence of Mammary Tumors Transmitted by Either Parent

Cited by 27 publications

References 6 publications

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐a^vyfb × c3h/sm mice

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐a^vyfb × c3h/sm mice

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

A Viral Aetiology for Breast Cancer: Time to Re-Examine the Postulate

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Strain C3H-A vy fB Mice: Ninety Percent Incidence of Mammary Tumors Transmitted by Either Parent

Cited by 27 publications

References 6 publications

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐avyfb × c3h/sm mice

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐avyfb × c3h/sm mice

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

A Viral Aetiology for Breast Cancer: Time to Re-Examine the Postulate

Contact Info

Product

Resources

About

Strain C3H-A ^vy fB Mice: Ninety Percent Incidence of Mammary Tumors Transmitted by Either Parent

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐a^vyfb × c3h/sm mice

Suppression of spontaneous mammary tumorigenesis despite mtv‐1 gene expression in hybrid and backcross c3h‐a^vyfb × c3h/sm mice