IDENTIFICATION OF A RETROVIRUS IN HUMAN BREAST CANCER

MELANA SM; DALES S; NEPOMNASCHY I; ROJOWSKY H; ABBOTT A; HOLLAND J; POGO B

California, USA

Congreso; International Workshop of Retroviral Pathogenesis; 2006

Cancer Research Institute, University of California

We have previously reported sequences homologous to the env gene of Mouse Mammary Tumor Virus (MMTV) but not to the human endogenous retrovirus in 38% of the 314 human breast cancers studied (Wang et al, Cancer Research 1995, 55: 5173). The sequences were absent from other human tissues; they were expressed in most of the positive breast specimens by RT PCR (Wang et al, Cl. Cancer Research 1998, 4:2565). The complete 9.9 Kb proviral sequence of an MMTV-like agent has been amplified and sequenced in two breast cancers (Liu, B. et al, Cancer Res 2001, 61:1754-9). Structural features of this provirus suggest that it is functional. We have looked for the presence of viral particles in primary cultures (MSSM) of env sequence positive tumors. The cells expressed env gene as shown by immunofluorescence and by western blot. FACS analysis indicated that between 5 to 10 % of the cells expressed the surface protein.  Retroviral particles budding from cells as well as in particulate fractions from culture media were observed by electron microscopy. Particulate fractions also display reverse transcriptase (RT) activity and the presence of all viral genes as detected by RT-PCR. The RT activity peaked at densities characteristic of retroviruses in sucrose gradients. None of these properties were observed in similar studies with normal breast primary cultures (HMEC) or established normal breast cell line (MCF10F). Co-culture of MSSM virus-producing and normal mammary epithelial cells (HMEC and MCF10F) demonstrated transfer of viral sequences as detected by PCR and by expression of env proteins by western blot, suggesting infectivity. Taken together, these findings support the identification of a human mammary tumor virus (HMTV) similar to MMTV in human breast.