JunD-mediated repression of GADD45α and γ regulates escape from cell death in prostate cancer

 Abstract

The AP-1 transcription factor complex has been implicated in a variety of biological processes including cell differentiation, proliferation, apoptosis and oncogenic transformation. We previously established that activation of the AP-1 family member JunD contributes to deregulated expression of the anti-apoptotic IL-6 gene in prostate cancer cells. We now show that inhibition of JunD in prostate cancer cells results in GADD45α- and γ-dependent induction of cell death and inhibition of tumor growth that is mediated at least partially via c-Jun N-terminal kinase (JNK) and p38 kinase activation. Apoptosis induction by dominant negative JunD and JNK and p38 kinase activation are impeded upon knock down of GADD45α and γ expression by small interfering RNA, most vividly demonstrating the central role of GADD45α and γ in JunD-mediated escape of prostate cancer cells from programmed cell death.

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Pages
2583 - 2591
doi
10.4161/cc.10.15.16057
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Report
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JunD-mediated repression of GADD45α and γ regulates escape from cell death in prostate cancer