IFNα induces the expression of the cyclin-dependent kinase inhibitor p21 in human prostate cancer cells

Abstract

Prostate cancer, like other types of cancer, is associated with the loss of cell cycle control, resulting in unregulated growth of cells. We report here on the inhibitory effects of interferon α (IFNα) on the cell cycle of prostate cancer cells, using the human prostate carcinoma cell line DU145 that has mutations in the tumor suppressor genes pRB, p53 and KAI1. IFNα inhibited growth and colony formation of DU145 cells and analysis by flow cytometry suggests that IFNα inhibited the progression of these cancer cells from the G₁ through S phase of the cell cycle. IFNα treatment of DU145 cells reduced cyclin dependent kinase 2 (cdk2) activity. In particular, cyclin E dependent cdk2 activity was inhibited by IFNα treatment. IFNα treatment, however, did not affect the amount of cdk2 bound to cyclin E. Consistent with this data, IFNα was able to induce expression of the kinase inhibitor p21 in DU145 cells. Furthermore, IFN treatment increased the amounts of p21 complexed with cdk2 in these cells. These data support a role for p21 in mediating the antiproliferative action of IFNα. The induction of p21 and its growth inhibitory effects in DU145 cells appears independent of p53, pRB and KAI1 status.