Mouse Mammary Tumor Virus-like RNA Transcripts and DNA Are Found in Affected Cells of Human Breast Cancer

Ford, Caroline; Faedo, Margaret; Rawlinson, William D.

doi:10.1158/1078-0432.ccr-04-0767

Cited by 41 publications

(33 citation statements)

References 28 publications

(30 reference statements)

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“…The major findings are as follows: (a) we have confirmed the presence of MMTV-like virus env gene sequences (using PCR and IHC) in ∼40% of human breast cancer specimens. Localization of the MMTV env sequences to the nuclei of breast cancer cells supports our previous report (35) …”

Section: Discussionsupporting

confidence: 91%

“…The localization of MMTV-like virus env by in situ PCR in breast DCIS and IDC specimens in which MMTV env sequences had previously been identified by standard PCR confirmed previous findings, some of which involved the same specimens (35). Although the immunohistochemicalbased data obtained with anti-gp52 antibodies is of interest, it has to be noted that previous studies have raised concern about the possibility of the presence of cross-reacting proteins leading to a positive signal, particularly those encoded by human endogenous retroviruses (36)(37)(38)(39).…”

Section: Validity Of the Datasupporting

confidence: 88%

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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: Discussionsupporting

confidence: 91%

Section: Validity Of the Datasupporting

confidence: 88%

Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

et al. 2010

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“…In a few studies, a prevalence of HERV transcripts, in particular class II elements, such as members of the HML-2 family, was reported for breast cancer tissues and cell lines (5,50,51). Recently, several reports described a novel human MMTVlike virus (HMLV) in human breast cancer that shares at least 95% sequence identity with MMTV, maintains open reading frames, has replicative potential, and is considered to be of exogenous origin (6,9,11,26,49). However, the limited reproducibility of original molecular observations has heated a highly controversial debate about the positive association of HMLV and human breast cancer (3,28,29,53,54).…”

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confidence: 99%

Variable Transcriptional Activity of Endogenous Retroviruses in Human Breast Cancer

Frank

Verbeke

Schwarz

et al. 2008

J Virol

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Human endogenous retroviruses (HERVs) account for up to 9% of the human genome and include more than 800 elements related to betaretroviruses. While mouse mammary tumor virus (MMTV) is the accepted etiological agent of mammary tumors in mice, the role of retroviral elements in human breast cancer remains elusive. Here, we performed a comprehensive microarray-based analysis of overall retroviral transcriptional activities in 46 mammary gland tissue specimens representing pairs of nonmalignant and tumor samples from 23 patients. An analysis of nonmalignant tissue samples revealed a distinct, mammary gland-specific HERV expression profile that consists of 18 constitutively active HERV taxa. For corresponding tumor samples, a general trend toward lower levels of HERV transcription was observed, suggesting common regulatory mechanisms. In various subsets of patients, however, increased transcript levels of single class I HERV families (HERV-T, HERV-E, and HERV-F) and several class II families, including HML-6, were detected. An analysis of transcribed HML-6 sequences revealed either the activation of some or the increased activity of several proviral loci. No evidence for MMTV or human MMTV-like virus transcripts was found, indicating that transcriptionally active, MMTV analogous, exogenous viruses were not present in the breast cancer samples analyzed.Great efforts have been invested in searching for the etiology of human breast cancer, a malignancy accounting for one-fifth of all female cancers worldwide. Although many studies have identified several risk factors, such as age, diet, hormonal balance, and genetic predisposition, a clear underlying cause for the disease, especially for sporadic cases of breast cancer, remains unknown. The current data suggest that breast cancer most likely is a multifactorial disease encompassing many different causes and factors (2, 30). Moreover, it has been suggested that an infectious agent contributes to the development of human breast cancer (16,45). Of note, a novel human retrovirus (xenotropic murine leukemia virus) has recently been associated with human prostate cancer (7, 48).Since type B mouse mammary tumor virus (MMTV) is the major etiological agent of mammary gland neoplasia in laboratory mice, researchers have searched extensively for a related human retrovirus that could be responsible for human breast cancer. The existence of such a virus, although postulated for many years, has not been conclusively demonstrated, although a long line of indirect evidence for it exists. This evidence is reflected by reports on the expression of type B envelope glycoprotein (gp52) (32) and the occurrence of virus-like particles in breast cancer biopsy specimens (8), in milk (38), and in cultures of breast cancer-derived cell lines (20, 40) as well as the detection of antibodies directed against gp52 in breast cancer patients (52). However, supporting observations have been confounded by a failure to continually observe virus particles in human tumors and by numerous controversial repo...

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“…Other workers using different methods have not reproduced our results, but none has then reported a faithful replication of our exact methodology (17)(18)(19). A recent report using in situ polymerase chain reaction localized the product and its expression by reverse transcription-polymerase chain reaction to epithelial cells, whereas stromal cells were negative (20).…”

mentioning

confidence: 54%