Reactive oxygen species regulate insulin-induced VEGF and HIF-1α expression through the activation of p70S6K1 in human prostate cancer cells

Qiong Zhou, Ling Zhi Liu, Beibei Fu, Xiaowen Hu, Xianglin Shi, Jing Fang, Bing Hua Jiang

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of angiogenesis. HIF-1 is composed of HIF-1α and HIF-1β subunits, and regulates VEGF expression at transcriptional level. In this study, we demonstrated that insulin induced H2O2 production and p70S6K1 activation in PC-3 prostate cancer cells. The inhibition of H2O2 production by catalase abolished insulin-induced p70S6K1 activation. H2O2 production is also required for insulin-induced VEGF and HIF-1α expression in the cells. Over-expression of p70S6K1 or HIF-1α reversed catalase- and rapamycin-inhibited VEGF transcriptional activation. These results suggest that insulin induced HIF-1α and VEGF expression through H2O2 production and p70S6K1 activation in prostate cancer cells. In addition, we found that inhibition of p70S6K1 by rapamycin decreased prostate tumor angiogenesis, suggesting that p70S6K1 plays an important role in tumor angiogenesis. These results provide some useful information for prostate cancer therapy in the future.

Original languageEnglish
Pages (from-to)28-37
Number of pages10
JournalCarcinogenesis
Volume28
Issue number1
DOIs
StatePublished - Jan 2007

Bibliographical note

Funding Information:
This work was supported by research grants 30570962 and 30470361 from National Natural Science Foundation of China; and by research grants from the Science and Technology Commission of Shanghai Municipality (04DZ14007 and 05DJ14009).

ASJC Scopus subject areas

  • Cancer Research

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