MCF-7 BREAST-CANCER CELLS TRANSFECTED WITH PROTEIN-KINASE C-ALPHA EXHIBIT ALTERED EXPRESSION OF OTHER PROTEIN-KINASE-C ISOFORMS AND DISPLAYA MORE AGGRESSIVE NEOPLASTIC PHENOTYPE

Increased protein kinase C (PKC) activity in malignant breast tissue a nd positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for t his signal transduction pathway in the pathogenesis and/or progression of breast cancer, To examine the role of PKC in the progression of br east cancer, human MCF-7 breast cancer cells were transfected with PKC -alpha and a group of heterogenous cells stably overexpressing PKC-alp ha were isolated (MCF-7-PKC-alpha). MCF-7-PKC-alpha cells expressed fi vefold higher levels of PKC-alpha as compared to parental or vector-tr ansfected MCF-7 cells. MCF-7-PKC-alpha cells also displayed a substant ial increase in endogenous expression of PKC-beta and decreases in exp ression of the novel delta- and eta-PKC isoforms. MCF-7-PKC-alpha cell s displayed an enhanced proliferative rate, anchorage-independent grow th, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells exhibited a significant reduction in estrogen receptor expressi on and decreases in estrogen-dependent gene expression, These findings suggest that the PKC pathway may modulate progression of breast cance r to a more aggressive neoplastic process.