1. P70S6K 1 regulation of angiogenesis through VEGF and HIF-1α expression
- Author
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Bian, Chuan-Xiu, Shi, Zhumei, Meng, Qiao, Jiang, Yue, Liu, Ling-Zhi, and Jiang, Bing-Hua
- Subjects
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REGULATION of neovascularization , *VASCULAR endothelial growth factors , *TRANSCRIPTION factors , *GENE expression , *RNA , *CANCER cell proliferation , *PROTEIN kinases , *PREVENTION ,TUMOR growth prevention - Abstract
Abstract: The 70kDa ribosomal S6 kinase 1 (p70S6K1), a downstream target of phosphoinositide 3-kinase (PI3K) and ERK mitogen-activated protein kinase (MAPK), is an important regulator of cell cycle progression, and cell proliferation. Recent studies indicated an important role of p70S6K1 in PTEN-negative and AKT-overexpressing tumors. However, the mechanism of p70S6K1 in tumor angiogenesis remains to be elucidated. In this study, we specifically inhibited p70S6K1 activity in ovarian cancer cells using vector-based small interfering RNA (siRNA) against p70S6K1. We found that knockdown of p70S6K1 significantly decreased VEGF protein expression and VEGF transcriptional activation through the HIF-1α binding site at its enhancer region. The expression of p70S6K1 siRNA specifically inhibited HIF-1α, but not HIF-1β protein expression. We also found that p70S6K1 down-regulation inhibited ovarian tumor growth and angiogenesis, and decreased cell proliferation and levels of VEGF and HIF-1α expression in tumor tissues. Our results suggest that p70S6K1 is required for tumor growth and angiogenesis through HIF-1α and VEGF expression, providing a molecular mechanism of human ovarian cancer mediated by p70S6K1 signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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