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Role of AKT/PKB signaling in fibroblast growth factor‐1 (FGF‐1)‐induced angiogenesis in the chicken chorioallantoic membrane (CAM)
Author(s) -
Forough Reza,
Weylie Brian,
Patel Chirag,
Ambrus Sandy,
Singh Ugra S.,
Zhu James
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20274
Subject(s) - angiogenesis , protein kinase b , fibroblast growth factor , chorioallantoic membrane , microbiology and biotechnology , biology , pi3k/akt/mtor pathway , transfection , cancer research , signal transduction , chemistry , biochemistry , gene , receptor
Transfection of chicken chorioallantoic membranes (CAMs) with a chimeric secreted version of fibroblast growth factor‐1 ( sp‐FGF‐1 ) gene construct leads to a significant increase in vascularization. Though FGF‐stimulated angiogenesis has been extensively studied, the molecular mechanisms regulating FGF‐1‐induced angiogenesis are poorly understood in vivo. This study was designed to investigate the role of the AKT (PKB) kinase signaling pathway in mediating sp‐FGF‐1‐induced angiogenesis in the chicken CAM. The involvement of the AKT pathway was demonstrated by up‐regulation of AKT1 mRNA expression in sp‐FGF‐1 compared to vector alone control transfected CAMs as demonstrated by real‐time RT‐PCR. Western analysis using an antibody specific to the activated AKT (phosphorylated AKT), demonstrated an increase in AKT activity in sp‐FGF‐1 compared to vector control transfected CAMs. More importantly, the AKT inhibitor ML‐9 significantly reduced sp‐FGF‐1‐induced angiogenesis in CAMs. These results indicate that AKT signaling plays a role in FGF‐1‐stimulated angiogenesis in vivo and the AKT pathway may serve as a therapeutic target for angiogenesis‐associated diseases. © 2004 Wiley‐Liss, Inc.