Forced expression of the interferon regulatory factor 2 oncoprotein causes polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cells

Rong Lin Xie, Andre J. Van Wijnen, Caroline M. Van der Meijden, Janet L. Stein, Gary S. Stein

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The IFN regulatory factor-2 (IRF-2) oncoprotein controls the cell cycle-dependent expression of histone H4 genes during S phase and may function as a component of an E2F-independent mechanism to regulate cell growth. To investigate the role of IRF-2 in control of cell proliferation, we have constructed a stable FDC-P1 cell line (F2) in which expression of IRF-2 is doxycycline (DOX)-inducible, and a control cell line (F0). Both the F2 and F0 cell lines were synchronized in the G1 phase by isoleucine deprivation, and IRF-2 was induced by DOX on release of cells from the cell cycle block. Flow cytometric analyses indicated that forced expression of IRF-2 has limited effects on cell cycle progression before the first mitosis. However, continued cell growth in the presence of elevated IRF-2 levels results in polyploidy (>4n) or genomic disintegration (<2n) and cell death. Western blot analyses revealed that the levels of the cell cycle regulatory proteins cyclin B1 and the cyclin-dependent kinase (CDK)-inhibitory protein p27 are selectively increased. These changes occur concomitant with a significant elevation in the levels of the FAS-L protein, which is the ligand of the FAS (Apo1/CD95) receptor. We also found a subtle change in the ratio of the apoptosis-promoting Bax protein and the antiapoptotic Bcl-2 protein. Hence, IRF-2 induces a cell death response involving the Fas/FasL apoptotic pathway in FDC-P1 cells. Our data suggest that the IRF-2 oncoprotein regulates a critical cell cycle checkpoint that controls progression through G2 and mitosis in FDC-P1 hematopoietic progenitor cells.

Original languageEnglish (US)
Pages (from-to)2510-2515
Number of pages6
JournalCancer research
Volume62
Issue number9
StatePublished - May 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Xie, R. L., Van Wijnen, A. J., Van der Meijden, C. M., Stein, J. L., & Stein, G. S. (2002). Forced expression of the interferon regulatory factor 2 oncoprotein causes polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cells. Cancer research, 62(9), 2510-2515.