p21 WAF1 is involved in interferon-β-induced attenuation of telomerase activity and human telomerase reverse transcriptase (hTERT) expression in ovarian cancer.
Telomerase activation is a key step in the development of human cancers. Interferon-β (IFN-β) signaling induces growth arrest in many tumors but the anticancer mechanism of IFN-β is poorly understood. In the present study, we show that IFN-β signaling represses telomerase activity and human telomerase reverse transcriptase (hTERT) transcription in ovarian cancer and suggest that this signaling is mediated by p21(WAF1). IFN-β triggered down-regulation of telomerase activity and hTERT mRNA expression and also induced p21 expression, independently of p53 induction. Ectopic expression of p21 attenuated hTERT promoter activity. Murine embryonic fibroblasts (MEFs) genetically deficient in p21 (p21-/-) showed elevated (> 15 times) hTERT promoter activity compared to wild-type MEFs. Overexpression of p21 reduced the hTERT promoter activity of p21-/- MEFs and hTERT mRNA expression in HCT119 p21(WAF1) null cell. These findings provide evidence that p21 is a potential mediator of IFN-β-induced attenuation of telomerase activity and tumor suppression.
Lee
Ji-Hae
JH
Department of Life Science, Yongin University, Yongin, 449-714, Korea.
Lee
Seung-Yeul
SY
Lee
Je-Ho
JH
Lee
Seung-Hoon
SH
D000818:Animals; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D016899:Interferon-beta; C509186:TERT protein, human; D019098:Telomerase