E2F1 induces tumor cell survival via nuclear factor-κB-dependent induction of EGR1 transcription in prostate cancer cells

Chaogu Zheng, Zijia Ren, Hetian Wang, Weici Zhang, Dhananjaya V. Kalvakolanu, Zhigang Tian, Weihua Xiao

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Transcription factor E2F1 has been implicated in both apoptosis-promoting and apoptosis-suppressing effects. However, factors that mediate its antiapoptotic effects are still not identified. Using prostate tumor-derived cell lines, we showed here that E2F1 activated the expression of transcription factor EGR1 for promoting cell survival. E2F1 up-regulated the production of EGR1-induced growth factors, epidermal growth factor, platelet-derived growth factor, and insulin-like growth factor II, which in turn activated the phosphoinosi- tide-3-kinase/Akt pathway to resist drug-induced apoptosis. Moreover, E2F1 directly induced the transcription of the Egrl gene using the κB site located in its proximal promoter. E2F1 physically interacted with the RelA subunit of nuclear factor-κB and modulated its transactivity to fully activate EGR1 transcription. Together, these studies uncovered a novel mechanism for E2Fl-induced suppression of apoptosis in prostate cancer.

Original languageEnglish (US)
Pages (from-to)2324-2331
Number of pages8
JournalCancer Research
Volume69
Issue number6
DOIs
StatePublished - Mar 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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