Activation of Src kinase in primary colorectal carcinoma: an indicator of poor clinical prognosis

Cancer
Heike AligayerGary E Gallick

Abstract

The specific activity of the non-receptor protein tyrosine kinase, Src, is increased in the majority of colon and rectal adenocarcinomas compared to normal mucosa. However, the prognostic significance of this difference is unknown. The objective of the current study was to determine if Src activity is a marker for poor clinical prognosis in colon carcinoma patients. As Src activation leads to expression of urokinase/plasminogen activator receptor (u-PAR), expression of Src and u-PAR were correlated with patient survival. Tumors and adjacent normal colonic mucosae from 45 patients with colorectal carcinoma were screened for Src activity by the immune complex kinase assay. Expression of u-PAR was determined by enzyme linked immunoabsorbent assay. The primary tumor-to-normal mucosa ratios of activity were compared following classification and regression tree (CART) analysis to determine the prognostic significance of elevated specific Src activity. Expression of u-PAR was correlated with Src activity. By CART analysis, Src activity in tumors elevated more than twofold over normal mucosa was significant. Increased Src activity significantly correlated with Dukes stage, pT and pN classification, and increased u-PAR levels (P < 0.001...Continue Reading

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