Pro-transforming growth factor-alpha processing in human colon carcinoma cells: Role of protein kinase C

✍ Scribed by Gadiraju Ramesh; Alan E. Levine

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 842 KB
• Volume: 62
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910620422

✦ Synopsis

The human colon cancer cell lines HCT I I 6 (poorly differentiated) and GEO (well differentiated) express the mitogenic peptide transforming growth factor alpha (TGF-a). The secretion of TGF-awas enhanced by phorbol 12-myristate 13-acetate (PMA), indicating the possible role of protein kinase C (PKC) in the formation of mature TGF-a. Cells were metabolically labeled with 35S-cysteine and the formation of the mature 6 kDa TGF-a polypeptide from the I7 kDa pro-TGF-a precursor was determined. The conversion of pro-TGF-a was complete in 2 4 hr with the HCT I 16 cells showing faster kinetics of TGF-cr formation than CEO cells. HCT I I 6 cells secreted more TGF-a than GEO cells and the rate and extent of formation of TGF-a was enhanced by PMA in both cell lines. The expression of several PKC isozymes by HCT I I 6 and GEO cells was examined by imrnunoblotting. The expression of all isozymes examined was higher in HCT I 16 cells compared with GEO cells. Calphostin C, an inhibitor of PKC, reduced the enzyme activity and significantly inhibited the PMA-induced secretion of TGF-a by both cell lines. Two agonists of PKC that act on specific PKC isozymes, thymeleatoxin and 12-deoxyphorbol I 3-phenylacetate 20-acetate (dPPA), stimulated the release of TGF-ol into the medium to the same extent as PMA. Since dPPA has been reported to stimulate PKC-PI specifically, our results suggest a potential role for PKC-P in the processing of pro-TGF-cr by these 2 human colon carcinoma cell lines.