ANALYSIS OF SIGNALING PROTEIN-KINASES IN HUMAN COLON OR COLORECTAL CARCINOMAS

Extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases are highly activated in an in vivo rat model of colorectal carcinogenesis. In addition, other protein kinases such as c-Src and c-Yes have been shown to be up-regul ated in some human colon cancers. To evaluate the activity of these ki nases in human colorectal carcinomas, we examined colon cancers and ad jacent normal intestinal mucosa from 11 patients. Moderate increases i n ERK and JNK activities, in addition to up-regulation of c-Src, p125( FAK) and tyrosine-phosphorylated proteins, were observed in a subset o f the colorectal carcinomas. There was a significant correlation found between levels of c-Src, p125(FAK), and tyrosine-phosphorylated prote ins, as well as between c-Src protein levels and JNK activity. This is the first report that examines several different kinases as markers t o characterize colorectal cancers in the same carcinoma sample, allowi ng the determination of correlations between markers in the same tumor s.