CCRK is a new candidate oncogene for colon cancer

Abstract

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Cell cycle related kinase (CCRK) is a newly identified cyclin-dependent kinase (CDK)-activating kinase (CAK). CCRK is indispensable for cell growth. Here we studied the expression profile of CCRK in colon tumor tissues by semi-quantitative RT-PCR. We found that 78% of the colon tumor tissues had an elevated level of CCRK expression, comparing with matched normal tissues. This result suggested that CCRK was involved in colon cancer tumorgenesis. Furthermore we found that CCRK was detectable in all cell lines derived from colon tumor, including p53 wild type cell lines (HCT116 and LoVo), and p53 mutant cell lines (colo205, DLD1, HT29, SW1116 and SW480). Suppression of CCRK by small interfering RNA (siRNA) significantly inhibited the proliferation of both LoVo and SW1116 cells. Flow cytometry analysis demonstrated that siCCRK caused a characteristic G1/S phase arrest, but no apoptosis, which is demonstrated by nuclear DAPI staining. In addition, we showed CCRK interacted with and activated cdk2/cyclin E complex, verified by co-immunoprecipitation. Immunofluorescence further showed that suppression of CCRK induced cytosolic translocation of cyclin E. Suppression of CCRK increased cisplatin-induced apoptosis in LoVo cells. In conclusion, our findings suggest CCRK is a new candidate oncogene and potentially a target for colon cancer therapy.