Mouse mammary tumor‐like env gene as a molecular marker for breast cancer?

Abstract

Dear Sir,The involvement of the mouse mammary tumor virus (MMTV) in breast cancer has long been postulated but never proven. Two studies have detected the sequence of the MMTV env gene in more than one-third of breast tumor tissues. 1,2 The present study was designed to investigate whether this viral sequence could serve as a molecular marker for the detection of breast cancer. We amplified the viral sequence in 2 cell lines and 18 breast tumor samples, using PCR, PCR Southern hybridization and real-time PCR. Surprisingly, we could not detect the viral sequence in any of these samples despite amplification in positive controls. Our study calls into question the role of MMTV in human breast cancer tumorigenesis.The involvement of retroviruses in human cancer was established long ago, e.g., HPV in cervical and oropharyngeal tumors. 3,4 The participation of a virus similar to MMTV in human breast cancer has long been postulated but never demonstrated. Several lines of evidence suggested the involvement of MMTV-like retroviruses in human breast cancer. Previously, it was shown that MMTV is an agent associated with a high incidence of breast cancer in mice. 5 Detectable MMTV env gene-related antigenic reactivity was found in tissue sections of breast cancer, 6 -10 breast cancer cell lines, 11 serum, 12,13 pleural effusion 14 and lymph nodes. 15 Moreover, sequence homology to MMTV has been found in human DNA. 1,2,16 -21 Two studies detected the env gene of MMTV in 37-38.5% of breast tumor tissues but only in 0 -2% of normal tissues. 1,2 According to these studies, this viral sequence was highly specific to breast tumor tissues and was not detected in other tumor tissues.The present study was designed to examine whether the env gene of MMTV could be used as a molecular marker for the detection of breast cancer. We planned to evaluate, by real-time PCR, a panel of normal tissues, tumor breast tissues and blood samples from 40 breast cancer patients. MMTV env gene plasmid and MCF-7 and MB-MDA-231 cell lines were used as a positive control, as described in previous studies. 1,2,11,17 The viral sequence was first amplified by regular PCR; then, PCR products were hybridized with an internal probe by PCR Southern hybridization; finally, real-time PCR was performed. We were unable to detect the viral sequence in the cell lines or in the breast tumor tissues despite robust amplification from the plasmid control. MATERIAL AND METHODS Cell lines and tumor tissuesThe MCF-7 and MB-MDA-231 cell lines were purchased from the ATCC (Manassas, VA) and grown in RPMI medium with FBS 10%, penicillin and streptomycin 1%.Eighteen invasive ductal carcinomas of the breast from 17 patients were collected at the

Progression from Normal Breast Pathology to Breast Cancer Is Associated with Increasing Prevalence of Mouse Mammary Tumor Virus-Like Sequences in Men and Women

“…We have independently reported the presence of MMTV-like sequences in 42% of Australian breast cancer samples and 1.8% of normal breast tissue samples (7), similar to the results in studies of American, Argentinian, and Italian women (1,2). However, there have recently been two small studies reporting the absence of MMTV-like sequences in breast tumors from Italian (8) and Austrian women (9). Although all other studies to date demonstrate strong associations between the presence of MMTV-like sequences and human breast cancer, no causal link has yet been shown.…”

Identification and characterization of human papillomavirus DNA sequences in Italian breast cancer patients by PCR and line probe assay reverse hybridization

“…A human equivalent of MMTV has been described in breast tumors, as well as in breast cancer cell lines (28). These results have been questioned and negated by others (29).…”

Mouse Mammary Tumor Virus Env–Derived Peptide Associates with Nucleolar Targets in Lymphoma, Mammary Carcinoma, and Human Breast Cancer

“…As the virus can cause both lymphoma and mammary carcinoma in mice, it is of special interest that one group reported the presence of such MMTV-related sequences in patients who have both breast cancer and lymphoma (10). However, this entire issue remains controversial, as other groups suggest, in studies based on gene amplification analysis, that MMTV-related sequences are not present in humans (28)(29)(30). We have approached this issue from a different angle, namely the level of expression of a virus-derived protein (p14), as we have the appropriate reagents available for such an analysis.…”