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Abstract
The identification of Mouse Mammary Tumour Virus (MMTV) as the causal factor for breast cancer in mice, initiated investigation into a viral cause for human breast cancer. MMTV-like virus has been detected in human breast cancers, lymphomas and primary biliary cirrhosis (PBC), suggesting the virus is not restricted to human breast cancers. We hypothesized that the virus is detected in human tissues influenced by steroid hormones.
We detected a region of the envelope (env) gene of MMTV-like virus in 53/210 (25%) of liver disease, 4/21 (19%) of hepatocellular carcinoma (HCC), 14/89 (16%) of ovarian cancer, 53/147 (36%) of prostate cancer, 5/50 (10%) of endometrial cancer and 13/141 (9%) of skin cancer samples but not in lung cancers (0/51). Viral env DNA was also detected in 4/81 (5%) of placentae and 5/90 (6%) of breast milk cells from healthy women whilst viral env RNA was detected in 2/90 (2%) of breast milk supernatants and (0/81) placentae. Immunohistochemistry staining for the presence of estrogen receptor alpha (ER-α) and progesterone receptor (PgR) demonstrated a significant association between ER-α/PgR and MMTV-like virus in human ovarian, prostate, endometrial and skin cancers though no significant association was observed between ER-α/PgR and the virus in liver tissues. We were also unable to demonstrate a significant association between accumulation of p53 tumour suppressor protein and MMTV-like virus in liver disease and HCC. Despite the demonstration of viral env integration in genomic DNA from human placentae using Southern Blots, other regions of the virus were not detected following PCR attempts with published primer sets.
This study adds to the current knowledge of distribution of MMTV-like virus in humans. The detection of the virus in hormonally influenced human tissues (positive for ER-α or PgR) indicates an association between MMTV-like virus and steroid hormones in some human tissues. The detection of the virus in placentae and breast milk also suggests potential routes of transmission of the virus in humans. Although the exact role of the virus in these tissues is not known, the presence of the virus together with other genetic alterations and/or the influence of steroid hormones could be involved in the transformation of various human tissues (i.e.pathogenesis).