Retinoid acid induced growth arrest of human breast carcinoma cells requires protein kinase Cα expression and activity

Retinoic acid inhibits proliferation of hormone-dependent, but not hormone-independent breast cancer cells. Retinoic acid-induced changes in cellular proliferation and differentiation are associated with disturbances in growth factor signaling and frequently with changes in protein kinase C expression. PKCδ, ε, and ζ are expressed in both hormone-dependent (T-47D) and hormone-independent (MDA-MB-231) cell lines. Retinoic acid arrested T-47D proliferation, induced PKCα expression and concomitantly repressed PKCζ expression. The changes in PKCα and PKCζ reflect retinoic acid-induced changes in mRNA. In contrast, retinoic acid had no effect on growth, or PKC expression in MDA-MB-231 cells. Growth arrest and the induction of PKCα, but not the reduction in PKCζ, resulted from selective activation of RARα. In total, these results support an important role for PKCα in mediating the anti-proliferative action of retinoids on human breast carcinoma cells.