Reduced C-terminal Src kinase activity is correlated inversely with pp60(c-src) activity in colorectal carcinoma

Cancer. 2001 Jul 1;92(1):61-70. doi: 10.1002/1097-0142(20010701)92:1<61::aid-cncr1292>3.0.co;2-d.

Abstract

Background: Specific kinase activity of the proto-oncogene product pp60(c-src) is reported to be elevated in patients with carcinoma of the colon, and a novel cytoplasmic protein-tyrosine kinase, C-terminal Src kinase (Csk), has been found to inactivate the members of the Src family protein-tyrosine kinase. In this study, Csk activity and pp60(c-src) activity were examined in colorectal tumors as well as in colon carcinoma cell lines.

Methods: Colorectal carcinoma tissue and adjacent nonneoplastic tissue from 24 patients, from 8 colon carcinoma cell lines, and from 1 normal colon cell line were used. The levels of pp60(c-src) and Csk in colorectal tissue and cell lines were analyzed by Western and/or Northern blot analysis, and their kinase activity levels were measured by in-gel kinase assay.

Results: In the samples from 24 patients with colorectal carcinoma, pp60(c-src) kinase activity and protein levels were increased by 7.8 +/- 0.55 and 2.6 +/- 0.13 times the control levels, respectively. Conversely, the Csk protein level and its kinase activity were reduced by 0.53 +/- 0.08 and 0.53 +/- 0.09 times the control levels, respectively. pp60(c-src) kinase activity was correlated inversely with Csk activity (correlation coefficient = -0.71; P < 0.0001). Of the cell lines, pp60(c-src) kinase activity and protein levels, respectively, were 7.4 +/- 1.22 and 1.86 +/- 0.28 times greater than normal control levels. Csk protein level and kinase activity, respectively, were 0.54 +/- 0.13 and 0.52 +/- 0.11 times less normal control levels and were correlated with mRNA amount.

Conclusions: Csk mRNA, protein, and its kinase activity were reduced in colorectal carcinoma and were correlated with pp60(c-src) kinase activity level. The reduced activity of Csk may be involved in the transformation of a subset of colorectal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blotting, Northern
  • CSK Tyrosine-Protein Kinase
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Female
  • HT29 Cells
  • Humans
  • Male
  • Middle Aged
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • RNA, Messenger / metabolism
  • Statistics as Topic
  • Tumor Cells, Cultured
  • src-Family Kinases

Substances

  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • Proto-Oncogene Proteins pp60(c-src)
  • src-Family Kinases
  • CSK protein, human