Abstract:
:Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of angiogenesis. HIF-1 is composed of HIF-1alpha and HIF-1beta 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-1alpha expression in the cells. Over-expression of p70S6K1 or HIF-1alpha reversed catalase- and rapamycin-inhibited VEGF transcriptional activation. These results suggest that insulin induced HIF-1alpha 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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Zhou Q,Liu LZ,Fu B,Hu X,Shi X,Fang J,Jiang BHdoi
10.1093/carcin/bgl085subject
Has Abstractpub_date
2007-01-01 00:00:00pages
28-37issue
1eissn
0143-3334issn
1460-2180pii
bgl085journal_volume
28pub_type
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