IFNalpha induces the expression of the cyclin-dependent kinase inhibitor p21 in human prostate cancer cells.
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 alpha (IFN alpha) 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. IFN alpha inhibited growth and colony formation of DU145 cells and analysis by flow cytometry suggests that IFN alpha inhibited the progression of these cancer cells from the G1 through S phase of the cell cycle. IFN alpha treatment of DU145 cells reduced cyclin dependent kinase 2 (cdk2) activity. In particular, cyclin E dependent cdk2 activity was inhibited by IFN alpha treatment. IFN alpha treatment, however, did not affect the amount of cdk2 bound to cyclin E. Consistent with this data, IFN alpha 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 IFN alpha. The induction of p21 and its growth inhibitory effects in DU145 cells appears independent of p53, pRB and KAI1 status.
Hobeika
A C
AC
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611, USA.
Subramaniam
P S
PS
Johnson
H M
HM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis*; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016898:Interferon-alpha; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases