Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/68436
標題: Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a critical role in the development of TGF beta resistance of H460 cell
作者: Lin, L.C.
Hsu, S.L.
Wu, C.L.
Liu, W.C.
Hsueh, C.M.
關鍵字: NSCLCs
TGF beta resistance
p(38)
PPAR gamma
Smad3
H460
growth-factor-beta
lung-cancer cells
carcinoma-cells
transforming
growth-factor-beta-1
epithelial-cells
expression
apoptosis
ligand
promotes
pathway
期刊/報告no:: Cellular Signalling, Volume 23, Issue 10, Page(s) 1640-1650.
摘要: The primary goal of the study was to investigate how peroxisome proliferator-activated receptor gamma (PPAR gamma) played a critical role in the protection of H460 cell, one of the non-small cell lung cancer (NSCLC) cells with multidrug resistance, from transforming growth factor beta (TGF beta)-mediated mitoinhibition. In the study. TGF beta resistance of H460 cell was first confirmed by analyses of PPAR gamma expression, its interaction with TGF beta-induced Smad3 and phospho-Smad3 (p-Smad3) and survival of H460. Results showed that enable to escape from G2/M phase arrest. H460 cell had higher resistance to TGF beta-mediated mitoinhibition than CH27 (a drug sensitive control). TGF beta significantly increased PPAR gamma expression of H460 but not of CH27 cell whereas nuclear accumulation of p-Smad3 was only limited to CH27, the latter was believed to contribute to the induction P(21) (waf1/cip1) and cyclin B1, cell cycle arrest at G2/M phase and TGF beta-mediated mitoinhibition of CH27 cell. TGF beta-incluced PPAR gamma of H460 cell was further demonstrated to bind to Smad3 and p-Smad3, and GW9662 (PPAR gamma inhibitor) or PPAR gamma-specific shRNA could disrupt the binding. GW9662 also increased the nuclear accumulation of p-Smad3 that eventually led to the reduction of TGF beta resistance of H460. A transient knockdown of PPAR gamma with shRNA revealed a similar effect as GW9662. In addition, activation of P(38) instead of ERK played a critical role in TGF beta-induced expression of PPAR gamma. which subsequently activated RhoA in H460 cell. (C) 2011 Elsevier Inc. All rights reserved.
URI: http://hdl.handle.net/11455/68436
ISSN: 0898-6568
文章連結: http://dx.doi.org/10.1016/j.cellsig.2011.05.018
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