Involvement of protein kinase C and an elastase-like enzyme in the processing of transforming growth factor-alpha in human colon carcinoma cell lines.
Human colon carcinoma cell lines secrete transforming growth factor-alpha (TGF-alpha). Previous work indicated that the apparent m.w. of the TGF-alpha secreted by these cells ranged between 5 and 25 kDa. The more differentiated GEO cell line secreted a higher percentage of high m.w. TGF-alpha than did the poorly differentiated HCT 116 cell line. In addition, the HCT 116 cells secreted 5-fold more TGF-alpha. Treatment of HCT 116 and GEO cells with a phorbol ester (TPA) resulted in a 4-fold increase in TGF-alpha in the conditioned media of both cell types. The TPA-induced release of TGF-alpha was blocked by an inhibitor of elastase-like enzymes. This suggested a role for protein kinase C (PKC) in TGF-alpha processing in colon carcinoma cells. Direct measurement of PKC activity indicated that the HCT 116 cells (which secrete more fully processed TGF-alpha) had 10-fold more PKC activity than GEO cells. The presence of an elastase-like activity in detergent extracts and the ability of an elastase inhibitor to block the TPA-induced secretion of TGF-alpha suggests that PKC and an elastase-like enzyme are involved in the processing and secretion of TGF-alpha by human colon carcinoma cell lines.
Levine
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AE
Department of Biological Chemistry, University of Texas-Houston 77225.
D003110:Colonic Neoplasms / Q000201:enzymology* / Q000378:metabolism*; D003902:Detergents; D004789:Enzyme Activation; D006801:Humans; D010196:Pancreatic Elastase / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D003902:Detergents; D011480:Protease Inhibitors; D016211:Transforming Growth Factor alpha; D011493:Protein Kinase C; D010196:Pancreatic Elastase; D013755:Tetradecanoylphorbol Acetate