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Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression.

Authors
Xia-C; Meng-Q; Ca-ZX; Shi-XL; Jiang-BH
Source
J Cell Physiol 2006 Oct; 209(1):56-66
NIOSHTIC No.
20030949
Abstract
Recent studies demonstrate that PI3K activation and PTEN mutation are frequently found in many human cancer cells and tissues. However, the mechanism of PI3K signaling in human cancer tumorigenesis remains to be elucidated. In this study we specifically downregulated p110alpha expression in ovarian cancer cells using siRNA interference. We found that p110alpha downregulation greatly decreased ovarian tumor growth and angiogenesis, and that p110alpha siRNA inhibited VEGF expression through decreasing hypoxia-inducible factor 1alpha expression in both ovarian cancer cells and tumor tissues. To determine the downstream targets of PI3K in regulating tumor growth and angiogenesis, we find that AKT1 is a major downstream mediator for regulating tumor growth, angiogenesis, and VEGF expression. These data show that p110alpha and AKT1 play an important role in tumor growth by inducing angiogenesis and by increasing HIF-1alpha and VEGF expression. This work provides a better understanding of the molecular mechanism of human cancer induced by the activation of PI3K signaling.
Keywords
Tumors; Tumorigens; Tumorigenesis; Cancer; Tumor-inhibition; Physiology
CODEN
JCLLAX
Publication Date
20061001
Document Type
Journal Article
Email Address
bhjiang@hsc.wvu.edu
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0021-9541
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Journal of Cellular Physiology
State
WV
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