Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Signaling through IFN regulatory factor-5 sensitizes p53-deficient tumors to DNA damage-induced apoptosis and cell death.

Hu G, Mancl ME, Barnes BJ

Division of Viral Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

Human IFN regulatory factor-5 (IRF-5) is a candidate tumor suppressor gene that mediates cell arrest, apoptosis, and immune activation. Here we show that ectopic IRF-5 sensitizes p53-proficient and p53-deficient colon cancer cells to DNA damage-induced apoptosis. The combination IFN-beta and irinotecan (CPT-11) cooperatively inhibits cell growth and IRF-5 synergizes with it to further promote apoptosis. The synergism is due to IRF-5 signaling since a striking defect in apoptosis and cell death was observed in IRF-5-deficient cells, which correlated well with a reduction in DNA damage-induced cellular events. Components of this IRF-5 signaling pathway are investigated including a mechanism for DNA damage-induced IRF-5 activation. Thus, IRF-5-regulated pathways may serve as a target for cancer therapeutics.

Published 16 August 2005 in Cancer Res, 65(16): 7403-12.
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