Mouse Mammary Tumor Virus-Like Viral Infection and Human Breast Cancer

Holland, James F.; Pogo, Beatríz G. T.

doi:10.1158/1078-0432.ccr-04-1234

Cited by 39 publications

(32 citation statements)

References 20 publications

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“…Seventy percent of the complete MMTV-like virus genome, identified in human breast cancer specimens and viral particles from human breast metastases, have been sequenced and shown to display 91% to 99% homology to MMTV from mouse mammary tumors (4)(5)(6). In a recent study, env and long terminal repeat sequences with >98% homology to those of MMTV have been identified in breast cancers that had occurred in a mother, father, and daughter of the same family, living under the same roof (7).…”

Section: Introductionmentioning

confidence: 99%

Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

et al. 2010

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Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings. Cancer Res; 70(9); 3576-85. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

et al. 2010

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“…Ever since the discovery of the mouse mammary tumor virus (MMTV) (Bittner, 1936(Bittner, , 1948; Staff of the Roscoe B. Jackson Memorial Laboratory in Bar Harbor, 1933), many efforts have been made to build a human BC model based on the mouse mammary tumor model, since MMTV is universally considered to be the etiologic agent in the vast majority of murine mammary cancer. Several independent laboratories Etkind et al, 2000Etkind et al, , 2004Ford et al, 2003Ford et al, , 2004aHolland and Pogo, 2004;Levine et al, 2004;Liu et al, 2001;Mason et al, 2004;Melana et al, 2001Melana et al, , 2002Wang et al, 1995Wang et al, , 1998Wang et al, , 2001Wang et al, , 2004Xu et al, 2003Xu et al, , 2004, but not others Cason, 2004, 2005;Mant et al, 2004a,b;Selmi et al, 2004;Witt et al, 2003), have detected sequences very closely related to MMTV in DNA isolated from human BC tumors. Additional studies suggest that betaretroviruses are present in a much wider range of species than previously known, including rodents, primates, and felines.…”

Section: Introductionmentioning

confidence: 99%

Of mice, cats, and men: Is human breast cancer a Zoonosis?

Szabo

Haislip

Garry

2005

Microscopy Res & Technique

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Mouse mammary tumor virus (MMTV), a member of the betaretroviridae, is the most common cause of breast cancer (BC) in mice. MMTV is transmitted in mice both in the germline as endogenous proviruses and exogenously as infectious virions. Here, we review a variety of evidence accumulated for six decades that has suggested that a human homologue of MMTV may exist. The findings include recent studies from several independent laboratories that have detected sequences very closely related to MMTV in DNA isolated from human BC tumors. Other laboratories, however, have failed to detect the MMTV-related sequences in human DNA samples, and conclusive evidence for a human mammary tumor virus has been elusive. We also reviewed additional studies, suggesting that betaretroviruses are present in a much wider range of species than previously known, including rodents, felines, and primates. The observation that a subset of cats may be infected with a close homologue of MMTV may be of epidemiological significance for human BC. Cats may become infected by MMTV from mice, and in turn may transmit the virus to humans, possibly after selection for variants with an expanded host range.

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“…There are, however, no published reports of anti-MMTV seropositivity among breast cancer patients in whom MMTV RNA expression was found, nor among those in whom DNA sequences resembling MMTV were found (Holland and Pogo, 2004). Likewise, there are no reports of MMTV DNA detection among such patients who were putatively MMTV seropositive.…”

Section: Discussionmentioning

confidence: 97%

“…During the past 10 years, molecular evidence of MMTV in human breast cancer tissue has been reported by a few laboratories using polymerase chain reaction (PCR) techniques (summarised in Holland and Pogo (2004)). These findings are controversial, because other laboratories have been unable to replicate detection of MMTV and because the DNA amplified by PCR in some laboratories has had homology with nonviral sequences in the human genome (summarised in Mant et al (2004)).…”

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confidence: 99%

Prevalence of serologic reactivity against four strains of mouse mammary tumour virus among US women with breast cancer

2006

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Mouse mammary tumour virus (MMTV) causes breast cancer in mice, and MMTV-specific antibodies develop to high titers among mice infected as adults. Whether MMTV or a related virus infects humans is uncertain, because MMTV DNA sequences have been detected inconsistently and because serologic methods have varied widely. The current study used immunoblot and immunoprecipitation with four strains of MMTV (RIII, FM, C3H, and LA) to detect specific antibodies in 92 sera from US women with breast cancer and in masked dilutions of monoclonal hybridoma and hyperimmunised goat positive-control reagents. In these positive controls, MMTV antibodies of the expected molecular weights were detected at high titer (1 : 100 in the monoclonal reagent, 1 : 10000 in the hyperimmunised goat serum). Nearly 30% of the sera from women with breast cancer had at least one faint band on an immunoblot, but none of these matched the molecular weight of bands revealed by probing the same blot strips with the goat serum. The goat serum readily immunoprecipitated MMTV antigens from all four strains of MMTV, but MMTV antigens were not immunoprecipitated by any of the six breast cancer sera that had four or more nonspecific immunoblot bands. Thus, among women with breast cancer, we found no MMTV-specific antibodies. The upper 95% confidence limit implies that MMTV seroprevalence among breast cancer patients does not exceed 3%.

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Mouse Mammary Tumor Virus-Like Viral Infection and Human Breast Cancer

Cited by 39 publications

References 20 publications

Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

Of mice, cats, and men: Is human breast cancer a Zoonosis?

Prevalence of serologic reactivity against four strains of mouse mammary tumour virus among US women with breast cancer

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