Increased transforming growth factor-alpha levels in human colon carcinoma cell lines over-expressing protein kinase C

Int J Cancer. 1999 Jan 5;80(1):72-7. doi: 10.1002/(sici)1097-0215(19990105)80:1<72::aid-ijc15>;2-0.


Transforming growth factor-alpha (TGF-alpha) is synthesized as a membrane-bound precursor protein, pro-TGF-alpha, that is converted to a soluble form by 2 endoproteolytic cleavages. Several factors have been implicated in the regulation of the second rate-limiting step, including protein kinase C (PKC). Earlier results indicated a potential role for the conventional class of PKC isozymes in the observed increase in TGF-alpha in the conditioned media of 2 human colon carcinoma cell lines. The present study addresses the potential role of specific PKC isozymes in this process using sense and anti-sense expression vectors for PKC isozymes. Two human colon carcinoma cell lines, HCT 116 and GEO, were transfected with plasmids, leading to the over-expression of PKC-alpha, -betaI or -betaII; and the secretion of TGF-alpha into the conditioned medium was determined. Over-expression of either PKC-betaI or PKC-betaII in these cell lines enhanced the levels of TGF-alpha in the media 2- to 5-fold. Over-expression of PKC-alpha did not alter the amount of TGF-alpha in the media to a significant extent. Transfection of HCT 116 cells with the anti-sense PKC-betaI cDNA resulted in a reduction in PKC-betaI protein expression. This was accompanied by a decrease in the amount of TGF-alpha in the conditioned media. Our results indicate that modulation of PKC-beta protein levels alters the amount of TGF-alpha found in the conditioned media from these colon carcinoma cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics*
  • Culture Media, Conditioned
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Protein Kinase C / biosynthesis
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Transfection
  • Transforming Growth Factor alpha / biosynthesis
  • Transforming Growth Factor alpha / genetics*
  • Tumor Cells, Cultured


  • Culture Media, Conditioned
  • Isoenzymes
  • Recombinant Proteins
  • Transforming Growth Factor alpha
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha