Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas.

Abstract

We examined the expression of p34cdc2 and its kinase activity in human gastric and colonic carcinoma cell lines and carcinoma tissues and studied its relation with a tumor-suppressor gene product, p53. All the gastric and colonic cancer cell lines expressed p34cdc2 and showed its kinase activity at various levels. When the cells were arrested in mitotic metaphase by the use of nocodazole, p34cdc2 kinase activity was induced and p53 was apparently phosphorylated. Of 12 gastric carcinoma cases, 11 (91.7%) showed higher p34cdc2 kinase activity in tumor tissues than in corresponding non-neoplastic mucosa. The protein kinase activities in the individual cases were well correlated with the levels of p34cdc2 protein expression. A good correlation was also found between the expression of p34cdc2 and proliferating cell nuclear antigen (PCNA). Almost all the colonic carcinomas showed higher cdc2 kinase activity and increased p34 expression when compared with non-neoplastic mucosa. Interestingly, most of the gastric and colonic carcinomas having high cdc2 kinase activity expressed high levels of p53. These findings suggest that the increased p34cdc2 kinase activity might cause the development and proliferation of gastric and colonic carcinomas, partly through abnormal p53 accumulation.