MCF-7 breast cancer cells transfected with protein kinase C-alpha 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-a, and a group of heterogenous cells stably over expressing PKC-a were isolated (MCF-7-PKC- a).MCF-7-PKC-a cells expressed five fold higher levels of PKC-a as compared to parental or vector-transfected MCF- 7 cels. MCF-7-PKC-a cells also displayed a substantial increase in endogenous expression of PKC-8 and decreases in expression of the novel 6- and q-PKC isoforms.

MCF-7-PKC-a 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- a 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. Originally published Journal of Clinical Investigation, Vol. 95, No. 4, Apr 1995