Alterations of Cell Cycle Regulatory Proteins in Lung Cancer

Abstract

With the discovery of cyclins and cydin-dependent kinases (cdk), key regulators of cell cyde, it is now possible to test whether the deregulation of any or all of these molecules could lead to oncogenesis. Information regarding the dinical significance of the cyclins and cdks is beginning to unfold. It has been found that certain cyclins or cdks are overexpressed in some tumor tissues including liver, parathyroid, and breast cancer. However, data on the expression of cyclins or cdks in lung cancer have not been reported. In this study, we examined the expression of cydins and cdks in various primary lung cancer tissues by Western blot analysis to determine if there was an altered expression in those tissues. Human lung cancer tissues consisted of 16 adenocarcinomas, 18 squamous cell carcinomas, 2 small cell carcinomas, 1 large cell cardnoma, and 1 with sarcoma. Western blot analysis showed that the levels of cyclin A and B1, and cdk2 expression were not elevated as compared to normal tissues. However, overexpression of cyclin Dl (8/38, 21%), cdk4 (8/38, 21%), and cdc2 (12/38, 32%) was observed in cancer tissues as compared to normal tissues. The expression of cyclin E was higher in all the cancer tissues tested than in normal tissues. These data implicate dysregulated expression of several cyclin and cdk genes, particularly cyclin E, as a potential factor in the pathogenesis of lung cancer.