Mouse mammary tumor virus-related sequences in Mus musculus genome and human breast cancer tissues

Abstract #3087 Background: Mouse mammary tumor virus is the causative agent for breast cancer (BC) in susceptible mouse lines. MMTV –homologous sequences were detected in breast carcinoma tissue DNA samples from 14-75% BC patients in Mexico, China, USA, Australia and Tunis. However, the sequences weren't found in Japanese, Austrian, English and some other human populations. Earlier, we have found the env MMTV –homologous sequences in BC tissues and peripheral blood lymphocyte DNA samples in 39-42% sporadic and 52% familial BC as well as in 64% of BC during pregnancy and/or lactation. These population differences in MMTV-related retrovirus frequencies might associated with geographic distribution of Mus musculus sp.domesticus – native MMTV reservoir. Material and methods: To demonstrate if wild commensal mice species are MMTV carriers we investigate 11 mice ( 3 males, 8 females) related to Mus musculus sp.domesticus from Moscow region (Russia) using specific PCR and RT-PCR followed by PCR products subcloning in pGEM-T vector and sequencing. A gp52 and ITAM-coding areas of the env MMTV gene, significant for MMTV infection and epithelial cells transformation , as well as a Sag-coding area of 3'LTR were analyzed. MMTV superantigen (Sag) – mediated amplification of MMTV in lymphoid cells is required for efficient viral transformation and dissemination in the mammary gland. Results: The sequences homologous to these functionally significant MMTV genome areas were detected in the DNA samples from mouse liver, timus and peripheral blood. In 63% (7/11) animals analyzed the sequences were expressed. The sequences homology with MMTV genome (C3H strain) according BLAST was 93-96%; homology with human MMTV- related provirus detected in BC patients was 86-95%. Recently MMTV-induced human epithelial cell transformation and important role of ITAM-coding area of the env MMTV gene was demonstrated in vitro. Conclusion: MMTV-related sequences were found in wild commensal mice, Mus musculus sp.domesticus, from Moscow region. In 60% cases these sequences, homologous to functionally significant env- and Sag-coding virus genome regions were expressed. Preliminary data support the possibility of the horizontal MMTV transmission from mice to humans, except of vertical one from mother to children. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3087.