E2F1 Induces Tumor Cell Survival via Nuclear Factor-B–Dependent Induction of EGR1 Transcription in Prostate Cancer Cells

¹Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, Peoples Republic of China and ²Marlene and Stewart Greenebaum Cancer Center, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland

^* To whom correspondence should be addressed. E-mail: xiaow{at}ustc.edu.cn.

	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 phosphoinositide-3-kinase/Akt pathway to resist drug-induced apoptosis. Moreover, E2F1 directly induced the transcription of the Egr1 gene using the B site located in its proximal promoter. E2F1 physically interacted with the RelA subunit of nuclear factor-B and modulated its transactivity to fully activate EGR1 transcription. Together, these studies uncovered a novel mechanism for E2F1-induced suppression of apoptosis in prostate cancer. [Cancer Res 2009;69(6):2324–31]

Key Words: E2F1, EGR1, Prostate cancer survival