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The authors have found that retroviral sequences with 85% to 95% homology to the mouse mammary tumor virus were present in 40% of the sporadic breast cancers of American women. These sequences were not found in normal breasts or other tumors. A whole proviral structure was detected in 2 tumors. Breast cancer cells in culture were shown to contain and shed betaretroviral particles. This virus was designated human mammary tumor virus (HMTV). The authors have investigated the presence of HMTV sequences in a variety of breast conditions and geographic locations. Here they report that inflammatory breast cancer from American women shows a higher incidence of viral sequences (71%) than sporadic breast cancers. Similar incidence has been found in inflammatory breast cancers from Tunisia, and in gestational breast cancers. Because these conditions represent highly invasive malignancies, it is concluded that HMTV is sometimes associated with a particularly malignant phenotype., (Copyright 2010 American Cancer Society.)

Mouse mammary tumor virus (MMTV) has been proven to induce mammary cancer in mice. MMTV-like env gene sequences have been detected in one-third of the human breast tumors studied. The whole proviral structure with 95% homology to MMTV was found in two human breast tumors and was designated as human mammary tumor virus (HMTV). HMTV viral particles with betaretroviral features have been isolated. In addition, a retrovirus called human betaretrovirus (HBRV), homologous to the mentioned retroviruses, has been isolated from tissues of patients with primary biliary cirrhosis. In this report, the expression of HMTV envelope (Env) and capsid (Ca) was detected in 10 primary cultures of human breast cancer containing HMTV sequences (MSSM) by Western blot and fluorescence activated cell sorting (FACS), using a panel of antibodies against HMTV Env, HBRV Env and Ca and the MMTV Env Gp36 and Ca P27 proteins. By contrast, HMTV proteins did not react with antibody against the MMTV Env Gp52 protein. All the antibodies detected MMTV proteins with exception of two out of four monoclonal antibodies against HMTV Env. Approximately 13% of the MSSM cells showed HMTV protein expression by FACS analysis. This report shows the expression of HMTV proteins for the first time in human breast cancer cells using a panel of antibodies against HMTV, HBRV and MMTV proteins. This should be taken into consideration when MMTV antibodies are used to detect HMTV proteins in human tissues.

Background: An early immunologic study suggesting that a virus similar to the mouse mammary tumor virus (MMTV) was associated highly with breast carcinoma in Tunisian patients, compared with patients in the United States, led the authors to examine different breast carcinoma populations by using more current molecular techniques., Methods: Thirty-nine paraffin blocks were selected for sequencing of the 250-base pair segment of the MMTV from patients with breast carcinoma who were seen and treated at the Institut Salah Azaiz in Tunisia. Fifteen of those blocks were examined under code by a second laboratory, which used a different methodology and was blinded to the results of the first laboratory, and 14 blocks were analyzed successfully., Results: The comparison of Tunisian patients and patients from other countries clearly showed a significantly higher proportion of tumors with MMTV-like sequences in the Tunisian series of patients. There was complete reproducibility of data between the two laboratories. Using the results from the first laboratory and similar studies from the literature, detection of the MMTV-like env gene sequence showed an important geographic pattern with a significantly higher percentage of positive patients with breast carcinoma in Tunisia (74%) compared with patients with breast carcinoma in the United States (36%), Italy (38%), Australia (42%), Argentina (31%), and Vietnam (0.8%), Conclusions: The findings provided increased evidence for a human breast carcinoma virus with geographic differences in prevalence. The geographic differences were compatible with studies of MMTV in wild mice; thus, the data were plausible biologically., (Copyright 2004 American Cancer Society.)

We previously reported a 660-bp mouse mammary tumor virus (MMTV)-like env gene sequence in approximately 38% of human breast cancer DNA, but not in normal breasts or other tumors. This MMTV-like env gene sequence was expressed in 66% of the env gene-positive human breast cancers. An entire proviral structure was identified in human breast cancer DNA with high homology to MMTV and low homology to known human endogenous retrovirus. MMTV-like long terminal repeat (LTR) sequences were also detected in 41.5% of human breast cancers. They contain hormone-responsive elements, TEF-1 family elements, and the open reading frame for the superantigen (SAg). We have now amplified and sequenced MMTV-like sag sequences from 10 human breast cancers, and we found that they are highly homologous to those of MMTV. However, deletions and insertions at the COOH-terminal of sag were observed. The immune function of the human MMTV-like LTR SAg was also investigated. The sag gene was cloned and expressed in a human B-cell line (Ramos). T-cell proliferation and cytokine releasing assays were performed after cocultivation of T cells with irradiated Ramos SAg-expressing cells. The results indicate that expression of the human SAg stimulates T-cell activation in vitro, as the mouse SAg does. Because the T-cell responses in vitro are considered similar to those in vivo, these results suggest that the human LTR SAg might also play a role in human breast carcinogenesis.

In the last years research on the possible viral etiology of human breast cancer has been revised. Previous studies have demonstrated the presence of a Mouse Mammary Tumor Virus (MMTV) env gene-like sequence in about 38% of breast cancers from American and Italian women; these sequences are generally absent in other tumors and in normal mammary tissue. In the present study we have analyzed the presence of a 250-bp sequence of the MMTV env gene in breast cancer biopsies from Argentine patients. The retroviral fragment was present in 31% (23/74) of the tumors, only in one normal mammary tissue and in none of the fibroadenomas analYzed. Peripheral blood mononuclear cells (PBMC) from 46 cancer patients were also analyzed; the sequence was found in 17% (2/12) of the PBMC from env positive tumor patients and in 3% (1/34) of the env negatives. The results from Argentine samples are similar to those from USA and Italy, where the breast cancer incidence is alike. These findings support the hypothesis of a viral agent involved in the genesis of this neoplasia and encourage the continuation of these studies.