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Overexpression of Protein Kinase C in MCF-10A Human Breast Cells Engenders Dramatic Alterations in Morphology, Proliferation, and Motility¹

Department of Chemistry and Biochemistry, Queens College, City University of New York, Flushing, New York 11367

A nonmetastatic human mammary epithelial cell line (MCF-10A) was engineered to overproduce protein kinase C (PKC) so as to investigate a role for this isoform in the metastatic phenotype. PKC transfectants (clone 26) expressed an 8-fold higher level of PKC protein without compensatory alterations in other isoforms. Clone 26 proliferated slowly (accumulating in G₁ of the cell cycle) but exhibited pronounced increases in motility and adhesion. Elevated expression of cell cycle inhibitor p27 and focal adhesion proteins was observed, whereas E-cadherin expression decreased to undetectable levels. These observations were consistent with the morphology of PKC transfectants (large, disaggregated, and flat, with lamellipodia and extensive actin fibers) and control cells (small, aggregated, and refractile). Treatment with PKC inhibitors or transfection of a dominant negative (dn) mutant of Rac1, but neither dn RhoA nor dn cdc42, reduced the motility of clone 26, implicating PKC catalytic activity and endogenous Rac1, respectively, in the PKC-induced phenotype. Overall, PKC overexpression suppresses proliferation while endowing MCF-10A cells with properties consistent with the metastatic phenotype.

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