PI3K-AKT Signaling Pathway Regulates TGF-β Signaling Pathway In Prostate Carcinoma Cell

Objective:To investigate the roll of PI3K-AKT pathway in regulating the TGF-βsignaling and antiproliferative effect induced by TGF-βin prostate cancer PC-3 cells.Methods:Growth arrest,cell cycle arrest,luciferase reporter assay,RT-PCR were done to explore the crosstalk between these two signaling pathways.Results:PI3K-AKT pathway inhibited TGF-βsignaling using TGF-βresponsive CAGA luciferase reporter.Activation of PI3K-AKT pathway by using insulin and transfecting AKT(WT) and AKT(Myr) inhibited TGF-βresponsive CAGA-luciferase,inhibition of PI3K-AKT pathway by using LY294002 and transfecting PTEN(WT) and AKT(AA) enchanced CAGA-luciferase.Inhibition of PI3K-AKT pathway by LY294002 promoted antiproliferative effect and cell cycle arrest induced by TGF-β.LY294002 enhanced the ability of TGF-βto downregulate cyclinD1 promoter activity.Activation of PI3K-AKT pathway by insulin and Inhibition of PI3K-AKT pathway by LY294002 did not change the expression of signaling molecules of TGF-βpathway.Conclusions PI3K-AKT pathway inhibit TGF-βsignaling especially the antiproliferative effect induced by TGF-β.these two pathways had crosstalk and this was important for the formation and development of prostate carcinoma.