Troglitazone inhibits cell proliferation by attenuation of epidermal growth factor receptor signaling independent of peroxisome proliferator-activated receptor γ  

作　　者：Xiaoqi Li Xuanming Yang Youli Xu Xuejun Jiang Xin Li Fajun Nan Hong Tang 

机构地区：[1]Center for Infection and Immunity and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2]Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China [3]Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Cell Research》2009年第6期720-732,共13页细胞研究（英文版）

摘　　要：Peroxisome proliferator-activated receptors （PPAR） belong to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. Recent results have shown that agonists of PPARy, such as troglitazone （TGZ）, can inhibit cell proliferation and promote cell differentiation independent of PPARy. In the present study, we provide evidence that TGZ may bind directly to EGFR and trigger its signaling and internalization independent of PPARγ. Detailed studies revealed that prolonged incubation with TGZ effectively attenuated EGFR signaling by targeting the receptor to the endo-lysosomal degradation machinery. Although the extracellular signal-regulated kinasesignaling pathway was transiently activated by TGZ in EGFR overexpressing cancer cells, inhibition of EGF-induced Akt phosphorylation most likely accounted for the growth arrest of tumor cells caused by TGZ at pharmacologically achievable concentrations. Therefore, we have provided a new line of evidence indicating that TGZ inhibits cell pro- liferation by promoting EGFR degradation and attenuating Akt phosphorylation.

关 键 词：EGFR PPARΓ TROGLITAZONE ENDOCYTOSIS growth arrest 

分 类 号：Q55[生物学—生物化学] Q959.4