RETINOIC ACID-INDUCED GROWTH ARREST OF HUMAN BREAST-CARCINOMA CELLS REQUIRES PROTEIN-KINASE C-ALPHA EXPRESSION AND ACTIVITY

Retinoic acid inhibits proliferation of hormone-dependent, but not hor mone-independent breast cancer cells. Retinoic acid-induced changes in cellular proliferation and differentiation are associated with distur bances in growth factor signaling and frequently with changes in prote in kinase C expression. PKC delta, epsilon, and zeta are expressed in both hormone-dependent (T-47D) and hormone-independent (MDA-MB-231) ce ll lines. Retinoic acid arrested T-47D proliferation, induced PKC alph a expression and concomitantly repressed PKC zeta expression. The chan ges in PKC alpha and PKC zeta reflect retinoic acid-induced changes in mRNA. In contrast, retinoic acid had no effect on growth, or PKC expr ession in MDA-MB-231 cells. Growth arrest and the induction of PKC alp ha, but not the reduction in PKC zeta, resulted from selective activat ion of RAR alpha. In total, these results support an important role fo r PKC alpha in mediating the anti-proliferative action of retinoids on human breast carcinoma cells. (C) 1997 Wiley-Liss, Inc.