BREAST CANCER ETIOLOGY, DETECTION, AND TREATMENT

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Expression of the human endogenous retrovirus called HERV-K has been studied in short-term primary human breast cancer cell lines and similar lines established from normal adjacent tissue. In two of five breast cancer lines, complete expression of all retroviral genes was observed. In contrast, expression of one or more HERV-K genes was seen in normal adjacent tissue lines, but expression of the pol gene was never observed. No HERV-K information was expressed in human smooth muscle cells, and only the protease gene was expressed in keratinocytes. Phytohemagglutinin-stimulated and unstimulated primary peripheral blood lymphocytes from normal donors occasionally showed expression of the long terminal repeat or protease genes, but never of env or pol-related sequences. The HERV-K family is more closely related to mouse mammary tumor virus than other human endogenous retroviruses. Therefore, the preferential expression of a complete HERV-K-related genome in two of five primary breast cancer cell lines, but not in control cells, suggests that further studies on the possible role of endogenous retroviruses in breast cancer are warranted. In this regard, sera of individuals with breast cancer and proliferative breast disease, and relatives of familial breast cancer patients appear to exhibit more reactivity to HERV-K peptides than sera of normal women and men. Additional serologic studies are ongoing. Further studies related to the biology of breast cancer cells include investigation of telomerase, the enzyme responsible for elongation of telomeres and believed to be involved in the immortalization of cancer cells. Telomerase activity has been assessed in breast cancer cell lines and is currently being purified. Availability of the purified enzyme will facilitate investigations of specific telomerase inhibitors for future therapy and development of immunologic reagents with potential utility in detection, diagnosis, and treatment of breast cancer and other malignancies. Finally, studies of HBL-100 epithelial cells, established from milk of a healthy woman, revealed the presence of Mason-Pfizer monkey virus (MP-MV) in some stocks of this line. MP-MV was shown to be independently acquired from the SV40 genome, which is responsible for the transformed phenotype of these cells. Neither MP-MV nor SV40 appears responsible for their progression in vitro to malignancy. Users of these cells should be aware of the MP-MV contaminant in some stocks.