Role of protein kinase C alpha in the induction of carcinoembryonic antigen by transforming growth factor beta 1.
Previous studies showed that transforming growth factor beta 1 (TGF beta 1) 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 PKC alpha isoform in the regulation of CEA and CEA-GLYs expression by TGF beta 1. Expression of PKC alpha antisense RNA, through transfection experiments with an antisense PKC alpha expression vector, resulted in down-modulation of PKC alpha RNA and protein expression. TGF beta 1 was unable to stimulate the expression and secretion of CEA in cells in which the expression of PKC alpha protein was substantially reduced. The ability of TGF beta 1 to stimulate the expression of the 95- and 55-kDa CEA-GLYs, however, was not affected. We therefore conclude that TGF beta 1 regulates the secretion and expression of CEA through a signal-transducing pathway associated with PKC alpha. TGF beta 1 may also regulate the expression of CEA-GLYs through signal-transducing pathways associated with other PKC isoforms.
Chakrabarty
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Division of Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Huang
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S
D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008970:Molecular Weight; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D051571:Protein Kinase C-alpha; D016372:RNA, Antisense / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D007527:Isoenzymes; D016372:RNA, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha