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

Abstract

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. 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. 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. 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.