Amplified CDK2 and cdc2 activities in primary colorectal carcinoma

Abstract

BACKGROUND. Cyclins are overexpressed in various malignancies, including carcinoma of the colorectum, esophagus, lung, larynx, and breast. However, to the authors' knowledge, the protein levels and activities of cyclin-dependent kinases (CDKs), which are the functional cyclin partners in the cell cycle, have not been investigated previously. METHODS. Eight samples of cancer tissue and adjacent normal tissue were taken horn 23 patients with Stage B2-C1 (AJCC/UICC Stage II-III) colorectal carcinoma during curative resection. The protein levels of cyclin and CDKs were determined by Western blot analysis. The activities of CDKs were determined by the phosphorylation amount using specific substrates after immunoprecipitations. RESULTS. The protein expression of cyclin (D1, D3, E, and A) and CDKs (CDK4, CDK2, and cdc2) was higher in primary colorectal carcinoma tissue than in adjacent normal tissue. Whereas only 3 of 8 patients had increased CDK4 activity in cancer tissue, 8 of 8 and 7 of 8 patients had increased CDK2 and cdc2 activities, respectively, in cancer tissue compared with adjacent normal tissue. However, there were no positive correlations among the pathologic staging or differentiation status and the increased ratio of cyclin protein, CDK protein, or CDK activity. CONCLUSIONS. These results indicate that significant activation of S and M phases of the cell cycle occurs in primary colorectal carcinoma. Cancer 1999;85:546-53, (C) 1999 American Cancer Society.