Activation of PPARγ increases PTEN expression in pancreatic cancer cells
Activation of PPARγ increases PTEN expression in pancreatic cancer cells
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DOI：
10.1016/s0006-291x(02)02983-2
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发表时间：
2003-01-31
影响因子：
3.1
通讯作者：
Evers, BM
中科院分区：
文献类型：
--
作者：
Farrow, B;Evers, BM
PI3K通路参与胰腺癌侵袭性和细胞凋亡抵抗。pparγ是一种配体激活的转录因子，具有抗炎和抗肿瘤作用；抑制肿瘤的机制尚不清楚。本研究的目的是检测PPARgamma的激活是否可以增加肿瘤抑制因子PTEN的表达并抑制PI3K的活性。用PPRE-luciferase构建体转染的AsPC-1人胰腺癌细胞，在PPARgamma配体处理后显示出增强的发光，表明存在功能性的PPARgamma蛋白。选择性PPARgamma配体罗格列酮增加了PTEN在AsPC-1细胞中的表达；与抑制PPARgamma激活的GW9662同时处理，阻止了PTEN蛋白水平的增加。磷酸化Akt水平随着PTEN水平的升高而降低，表明PI3K活性受到抑制。综上所述，我们的研究结果表明PPARgamma的激活可能代表了一种通过增加PTEN水平和抑制PI3K活性来治疗胰腺癌的新方法。(C) 2002 Elsevier Science （USA）。版权所有。
The PI3K pathway contributes to the invasive properties and apoptosis resistance that epitomize pancreatic cancers. PPARgamma is a ligand-activated transcription factor with anti-inflammatory and anti-tumor effects; the mechanisms of tumor suppression are unknown. The purpose of this study was to examine whether activation of PPARgamma can increase the expression of the tumor suppressor PTEN and inhibit PI3K activity. AsPC-1 human pancreatic cancer cells, transfected with a PPRE-luciferase construct, demonstrated increased luminescence following treatment with PPARgamma ligands, indicating the presence of functional PPARgamma protein. The selective PPARgamma ligand rosiglitazone increased PTEN expression in AsPC-1 cells; concurrent treatment with GW9662, which inhibits PPARgamma activation, prevented the increase in PTEN protein levels. Levels of phosphorylated Akt decreased as PTEN levels increased, indicating inhibition of PI3K activity. Taken together, our results suggest that activation of PPARgamma may represent a novel approach for the treatment of pancreatic cancer by increasing PTEN levels and inhibiting PI3K activity. (C) 2002 Elsevier Science (USA). All rights reserved.