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Cell Growth & Differentiation Vol. 10, 343-352, May 1999
© 1999 American Association for Cancer Research

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

Xiao-guang Sun and Susan A. Rotenberg2

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{alpha} (PKC{alpha}) so as to investigate a role for this isoform in the metastatic phenotype. PKC{alpha} transfectants (clone 26{alpha}) expressed an 8-fold higher level of PKC{alpha} protein without compensatory alterations in other isoforms. Clone 26{alpha} 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{alpha} 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{alpha}, implicating PKC{alpha} catalytic activity and endogenous Rac1, respectively, in the PKC{alpha}-induced phenotype. Overall, PKC{alpha} overexpression suppresses proliferation while endowing MCF-10A cells with properties consistent with the metastatic phenotype.




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