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Carcinogenesis Advance Access published online on June 13, 2006

Carcinogenesis, doi:10.1093/carcin/bgl085
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received January 8, 2006
Revised May 8, 2006
Accepted May 16, 2006

CANCER BIOLOGY

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

Qiong Zhou 1 *, Ling-Zhi Liu 1 *, Beibei Fu 1, Xiaowen Hu 1, Xianglin Shi 1, Jing Fang 1, and Bing-Hua Jiang 2 *

1 The Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2 The Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Mary Babb Randolph Cancer Center, and Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506, USA

* To whom correspondence should be addressed.
Bing-Hua Jiang, E-mail: bhjiang{at}sibs.ac.cn


   Abstract

Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of angiogenesis. HIF-1 is composed of HIF-1{alpha} and HIF-1{beta} 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-1{alpha} expression in the cells. Over-expression of p70S6K1 or HIF-1{alpha} reversed catalase- and rapamycin-inhibited VEGF transcriptional activation. These results suggest that insulin induced HIF-1{alpha} 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.


* These two authors contributed equally to this work.
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