Elevated c-yes tyrosine kinase activity in premalignant lesions of the colon

The cellular oncogene c-yes and its viral homologue v-yes (the transforming gene of Yamaguchi 73 and Esh avian sarcoma viruses) encode 62-kilodalton, cytoplasmic, membrane-associated, protein-tyrosine kinases. For the related Src kinase, a close correlation exists between elevated kinase activity and cell transformation. Previously, we observed elevated Yes activity in many human colon carcinomas. Colonic neoplasia provides an opportunity to study tumor progression because most carcinomas arise from adenomas, which in turn arise from normal epithelia. The malignant potential of adenomas varies with size, histology, and degree of dysplasia. Large adenomas (> or = 2 cm) with villous architecture and severe dysplasia are most likely to develop carcinoma.

To determine whether Yes is activated in premalignant lesions of the colon, we measured its in vitro protein-tyrosine kinase activity in 21 colonic adenomas from 17 patients.

Activity of Yes in adenomas at greatest risk for cancer was significantly greater (12- or 14-fold as measured by enolase or autophosphorylation, respectively) than activity in adjacent normal mucosa. Moreover, villous structure, large size (> or = 2 cm), or severe dysplasia correlated with elevated Yes activity.

The activity of Yes is elevated in adenomas that are at greatest risk for developing cancer.