E2F1 Induces tumor cell survival via nuclear factor-kappaB-dependent induction of EGR1 transcription in prostate cancer cells.
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 kappaB site located in its proximal promoter. E2F1 physically interacted with the RelA subunit of nuclear factor-kappaB 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].
Zheng
Chaogu
C
Hefei 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.
Ren
Zijia
Z
Wang
Hetian
H
Zhang
Weici
W
Kalvakolanu
Dhananjaya V
DV
Tian
Zhigang
Z
Xiao
Weihua
W
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D050687:E2F1 Transcription Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D051996:Transcription Factor RelA / Q000378:metabolism
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D005472:Fluorouracil