BREAST CANCER ETIOLOGY, DETECTION, AND TREATMENT

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The human endogenous retrovirus type K(HERV-K), present at about fifty copies in the genome, appears to be a complete retrovirus with open reading frames encoding gag, pol, and env proteins and a central open reading frame encoding a putative regulatory protein. We have been investigating a possible association of HERV-K with human breast cancer largely due to its homology with mouse mammary tumor virus which causes mammary cancer in mice. Using novel short- term breast cancer cell strains, we have examined HERV-K mRNA expression by reverse transcriptase- polymerase chain reaction (RT-PCR) and northern blotting and have observed expression of all viral genes. In addition, some breast tumor cell strains exhibited retroviral RT activity by a highly sensitive PCR-enhanced assay. Whether this activity is encoded by HERV-K remains to be determined. We have examined paired tissue specimens of breast tumor and matched normal adjacent tissue for novel HERV-K integration sites and altered DNA methylation patterns which might suggest a mechanism whereby expression of HERV-K could also lead to expression of adjacent cellular oncogenes. A HERV-K-related DNA fragment seen in a breast tumor specimen but not in normal DNA from the same individual is currently being cloned and may prove useful as a probe for further HERV-K associations in other breast tumors. As an additional probe for a HERV-K-breast cancer association, we have examined patient sera for antibodies to HERV-K gag and envelope antigens in peptide-based enzyme-linked immunosorbent assays. Preliminary studies showed greater antibody reactivity in sera from breast cancer patients in Tunisia where very aggressive disease resembling inflammatory breast cancer is prevalent. Currently, studies on coded serum samples obtained from women in the U.S. with breast cancers of different types and stages are being carried out in order to verify if HERV-K is associated with a particular breast cancer. This information not only could link the endogenous virus with the cancer, but could also lead to development of simple diagnostic tests.