COEXPRESSION OF CDK2 CDC2 AND RETINOBLASTOMA GENE-PRODUCTS IN COLORECTAL-CANCER/

The retinoblastoma gene (Rb gene) is a tumour-suppressor gene and its product (pRB) is known to act as a negative regulator of the cell cycl e. Although lack of pRB expression resulting from gene alterations is considered to be responsible for the genesis of several human malignan cies, increased expression of pRB has been demonstrated in a majority of colorectal cancer cases. In the present study, we investigated the expression of pRB as well as that of its related kinases, cdk2 and cdc 2, in colorectal cancer, since these kinases have been reported to pho sphorylate and inactivate pRB. Western blot analysis revealed that col orectal cancer expressed higher levels of cdk2 and cdc2 than did norma l mucosa and that the ratio of the hyperphosphorylated form of PRE was higher in colorectal cancer. Furthermore, immunohistochemical studies showed that cdk2/cdc2 was expressed exclusively in the cancer cells p ositive for pRB. These results suggest that an increase in the express ion of cdk2/cdc2 in colorectal cancer may have prevented pRB from brak ing the cell cycle through phosphorylation.