Role of protein kinase cα in the induction of carcinoembryonic antigen by transforming growth factor β

Abstract

Previous studies showed that transforming growth factor b̃ (TGFb̃1) regulates the expression of carcinoembryonic antigen (CEA) and CEA-cross-reactive glycoproteins (CEA-GLYs) in human colon carcinoma cells through a signal-transducing pathway associated with protein kinase C (PKC) (Chakrabarty, J. Cell. Physiol., 1992, 152 494–499). In this study we determined the role of the PKCα isoform in the regulation of CEA and CEA-GLYs expression by TGFb̃1. Expression of PKCα antisense RNA, through transfection experiments with an antisense PKCα expression vector, resulted in down-modulation of PKCα RNA and protein expression. TGFb̃1 was unable to stimulate the expression and secretion of CEA in cells in which the expression of PKCα protein was substantially reduced. The ability of TGFb̃1 to stimulate the expression of the 95- and 55-KDa CEA-GLYs, however, was not affected. We therefore conclude that TGFb̃1 regulates the secretion and expression of CEA through a signal-transducing pathway associated with PKCα. TGFb̃1 may also regulate the expression of CEA-GLYs through signal-transducing pathways associated with other PKC isoforms.