Interferon induction of the tumor suppressor p21 inhibits cell cycle of tumor cells

Conference Paper

Type I and type II interferons (IFNs) are known to exert anticellular activity on a variety of cell types. We report here on the inhibitory effects of Interferon alpha (IFNa) and interferon gamma (IFN-y) on the cell cycle of the human prostate cancer cell line DU 145 that is defective in the retinoblastoma (RB) and p53 tumor suppressor gene products. These cells are sensitive to the antiproliferative effects of both IFNa and IFN-y and analysis by flow cytometry suggests that IFN acts specifically at the G1 to S phase transition. We have found that the mechanism behind this anticellular activity involves the cyclin dependent kinase (cdk) inhibitor p21. Both IFNa and IFNy cause an increase in p21 protein levels in DU145 cells. Further, this involvement of p21 in IFN regulation of the cell cycle is unique since other cdk inhibitors such as p27, p18, and p16 do not show similar increases in response to IFN treatment. In addition, the protooncogene c-myc, a potential downstream target of p21, is downregulated in response to IFN. Thus, IFNa and IFNy inhibit the DU145 cell cycle through p21 induction and c-myc downregulation independently of p53 and pRB status. Supported by grants #CA38587 and #CA69959 (to H.M.J.) from NIH.

Duke Authors

Cited Authors

  • Hobeika, AC; Subramaniam, PS; Johnson, HM

Published Date

  • December 1, 1997

Published In

Volume / Issue

  • 11 / 9

International Standard Serial Number (ISSN)

  • 0892-6638

Citation Source

  • Scopus