IFNγ inhibition of cell growth in glioblastomas correlates with increased levels of the cyclin dependent kinase inhibitor p21(WAF1/CIP1)

Scott Kominsky, Howard M. Johnson, Gail Bryan, Taishi Tanabe, Amy C. Hobeika, Prem S. Subramaniam, Barbara Torres

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma is a highly aggressive form of brain cancer characterized by uncontrolled cell growth resulting from a loss of cell cycle regulation. In this study we determined the antiproliferative effects of interferon gamma (IFNγ) on the glioblastoma cell lines T98G, SNB-19 and U-373, focusing on the ability of IFNγ, to increase levels of p21(WAF1/CIP1), an important negative regulator of cell cycle events. IFNγ was found to inhibit the growth of all cell lines, with inhibition ranging from 82.2% to 45.4%. Flow cytometry analysis showed that IFNγ treatment caused a cell cycle delay in the G1 or S phases. The strength of this delay varied, correlating with the degree by which IFNγ inhibited proliferation of each cell line. IFNγ treatment increased the production of the cyclin dependent kinase inhibitor (CKI) p21(WAF1/CIP1) in all cell lines, the level and kinetics of production of which correlated with the degree and stage of inhibition of cellular proliferation. Further, immunoprecipitation of p21(WAF1/CIP1) in complexes of p21(WAF1/CIP1)/cyclin-dependent kinase 2 (cdk2)/cyclin showed that the amount of p21(WAF1/CIP1) in the complexes and the inhibition of cdk2-cyclin kinase activity correlated with the level of p21(WAF1/CIP1) produced in the cells by IFNγ. These results show that IFNγ has significant antiproliferative effects on the glioblastoma cell lines and suggest that p2(WAF1/CIP1) plays a role in mediating these effects.

Original languageEnglish (US)
Pages (from-to)2973-2979
Number of pages7
JournalOncogene
Volume17
Issue number23
DOIs
StatePublished - Dec 10 1998
Externally publishedYes

Keywords

  • Cyclin dependent kinase 2
  • Glioblastoma
  • Interferon γ
  • p21(WAF1/CIP1)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint

Dive into the research topics of 'IFNγ inhibition of cell growth in glioblastomas correlates with increased levels of the cyclin dependent kinase inhibitor p21(WAF1/CIP1)'. Together they form a unique fingerprint.

Cite this