Protein kinase Calpha controls the adhesion but not the antiproliferative response of human colon carcinoma cells to transforming growth factor beta1: identification of two distinct branches of post-protein kinase Calpha adhesion signal pathway.
Transforming growth factor beta1 (TGFbeta1) 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 TGFbeta1-responsive human colon carcinoma cells. Exactly how TGFbeta1 controls cellular adhesion and proliferation is poorly understood. In the present report, we showed that down-regulating protein kinase Calpha (PKCalpha) expression blocked the induction of these adhesion responses by TGFbeta1, showing that PKCalpha is a postreceptor focal point controlling the induction of these molecules. Down-regulating PKCalpha expression, however, had minimal effect on the antiproliferative response to TGFbeta1 or the induction of p21/WAF1, a marker associated with the antiproliferative effect of TGFbeta1, 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 postPKCalpha adhesion signal pathways, one leading to the induction of LM and the other leading to the induction of FN and CEA.
Chakrabarty
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S
Department of Laboratory Medicine, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Rajagopal
S
S
Moskal
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TL
D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D007797:Laminin / Q000096:biosynthesis; D011493:Protein Kinase C / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D005353:Fibronectins; D007527:Isoenzymes; D007797:Laminin; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C