MCF-7 breast cancer cells transfected with protein kinase C-α exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype

Abstract

Increased protein kinase C (PKC) activity in malignant breast tissue and positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for this signal transduction pathway in the pathogenesis and/or progression of breast cancer. To examine the role of PKC in the progression of breast cancer, human MCF-7 breast cancer cells were transfected with PKC-α and a group of heterogenous cells stably overexpressing PKC-α were isolated (MCF-7-PKC- α). MCF-7-PKC-α cells expressed fivefold higher levels of PKC-α as compared to parental or vector-transfected MCF-7 cells. MCF-7-PKC-α cells also displayed a substantial increase in endogenous expression of PKC-β and decreases in expression of the novel δ- and η-PKC isoforms. MCF-7-PKC-α cells displayed an enhanced proliferative rate, anchorage-independent growth, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-α cells exhibited a significant reduction in estrogen receptor expression and decreases in estrogen-dependent gene expression. These findings suggest that the PKC pathway may modulate progression of breast cancer to a more aggressive neoplastic process.