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 Two Distinct Branches Of Post-Protein Kinase C Alpha Adhesion Signal Pathway

Transforming growth factor beta 1 (TGF beta 1) inhibits cellular proliferation and induces the expression of the matrix adhesion molecules fibronectin (FN) and laminin (LM) in a concurrent manner, followed by the induction of the intercellular adhesion molecule carcinoembryonic antigen (CEA) (collectively designated as adhesion responses) in TGF beta 1-responsive human colon carcinoma cells. Exactly how TGF beta 1 controls cellular achesion and proliferation is poorly understood. in the present report, we showed that down-regulating protein kinase C alpha (PKC alpha) expression blocked the induction of these adhesion responses by TGF beta 1, showing that PKC alpha is a postreceptor focal point controlling the induction of these molecules. Down-regulating PKC alpha expression, however, had minimal effect on the antiproliferative response to TGF beta 1 or the induction of p21/NAF1, a marker associated with the antiproliferative effect of TGF beta 1, demonstrating that the adhesion signal pathway is distinct from that of antiproliferation. Blockade of FN induction blocked the induction of CEA but not the induction of LM. Blockade of LM induction, on the other hand, had no effect on the induction of FN and CEA. These results established the existence of two distinct and parallel postPKC alpha adhesion signal pathways, one leading to the induction of Lm and the other leading to the induction of FN and CEA.