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-regulated in some human colon cancers. To evaluate the activity of these kinases in human colorectal carcinomas, we examined colon cancers and adjacent normal intestinal mucosa from 11 patients. Moderate increases in ERK and JNK activities, in addition to up-regulation of c-Src, p125FAK, and tyrosine-phosphorylated proteins, were observed in a subset of the colorectal carcinomas. There was a significant correlation found between levels of c-Src, p125FAK, and tyrosine-phosphorylated proteins, as well as between c-Src protein levels and JNK activity. This is the first report that examines several different kinases as markers to characterize colorectal cancers in the same carcinoma sample, allowing the determination of correlations between markers in the same tumors.