PROTEIN-KINASE-C-ALPHA CONTROLS THE ADHESION BUT NOT THE ANTIPROLIFERATIVE RESPONSE OF HUMAN COLON-CARCINOMA CELLS TO TRANSFORMING-GROWTH-FACTOR BETA-1 - IDENTIFICATION OF 2 DISTINCT BRANCHES OF POST-PROTEIN KINASE C-ALPHA ADHESION SIGNAL PATHWAY

Transforming growth factor beta 1 (TGF beta 1) inhibits cellular proli feration and induces the expression of the matrix adhesion molecules f ibronectin (FN) and laminin (LM) in a concurrent manner, followed by t he induction of the intercellular adhesion molecule carcinoembryonic a ntigen (CEA) (collectively designated as adhesion responses) in TGF be ta 1-responsive human colon carcinoma cells. Exactly how TGF beta 1 co ntrols cellular achesion and proliferation is poorly understood. in th e present report, we showed that down-regulating protein kinase C alph a (PKC alpha) expression blocked the induction of these adhesion respo nses by TGF beta 1, showing that PKC alpha is a postreceptor focal poi nt controlling the induction of these molecules. Down-regulating PKC a lpha expression, however, had minimal effect on the antiproliferative response to TGF beta 1 or the induction of p21/NAF1, a marker associat ed with the antiproliferative effect of TGF beta 1, demonstrating that the adhesion signal pathway is distinct from that of antiproliferatio n. Blockade of FN induction blocked the induction of CEA but not the i nduction of LM. Blockade of LM induction, on the other hand, had no ef fect on the induction of FN and CEA. These results established the exi stence of two distinct and parallel postPKC alpha adhesion signal path ways, one leading to the induction of Lm and the other leading to the induction of FN and CEA.