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PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesis.

Authors
Fang-J; Ding-M; Yang-LL; Liu-LZ; Jiang-BH
Source
Cell Signal 2007 Dec; 19(12):2487-2497
NIOSHTIC No.
20032974
Abstract
PI3K pathway exerts its function through its downstream molecule AKT in regulating various cell functions including cell proliferation, cell transformation, cell apoptosis, tumor growth and angiogenesis. PTEN is an inhibitor of PI3K., and its loss or mutation is common in human prostate cancer. But the direct role and mechanism of PI3K/PTEN signaling in regulating angiogenesis and tumor growth in vivo remain to be elucidated. In this study, by using chicken chorioallantoic membrane (CAM) and in nude mice models, we demonstrated that inhibition of PI3K activity by LY294002 decreased PC-3 cells-induced angiogenesis. Reconstitution of PTEN, the molecular inhibitor of PI3K in PC-3 cells inhibited angiogenesis and tumor growth. Immunohistochemical staining indicated that PTEN expression suppressed HIF-1 alpha, VEGF and PCNA expression in the tumor xenographs. Similarly, expression of AKT dominant negative mutant also inhibited angiogenesis and tumor growth, and decreased the expression of HIF-1 alpha and VEGF in the tumor xenographs. These results suggest that inhibition of PI3K signaling pathway by PTEN inhibits tumor angiogenesis and tumor growth. In addition, we found that AKT is the downstream target of PI3K in controlling angiogenesis and tumor growth, and PTEN could inhibit angiogenesis by regulating the expression of HIF-1 and VEGF expression through AKT activation in PC-3 cells.
Keywords
Men; Tumor-inhibition; Tumorigenesis; Laboratory-animals; Laboratory-testing; Cell-biology; Cell-alteration; Cell-function; Cell-growth; Cell-metabolism; Cell-transformation; Cellular-function; Cellular-reactions; Chemical-binding; Chemical-reactions; Immunochemistry; Immune-reaction
Contact
Bing-Hua Jiang, Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506-9300
CODEN
CESIEY
Publication Date
20071201
Document Type
Journal Article
Email Address
bhjiang@hsc.wvu.edu
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
12
ISSN
0898-6568
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Cellular Signalling
State
WV
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