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学科主题: 临床医学
题名:
BRG1 promotes chemoresistance of pancreatic cancer cells through crosstalking with Akt signalling
作者: Liu, Xiaoran1; Tian, Xiaodong1; Wang, Feng1; Ma, Yongsu1; Kornmann, Marko2; Yang, Yinmo1
关键词: Pancreatic cancer ; BRG1 ; Akt phosphorylation ; Gemcitabine ; Chemoresistance
刊名: EUROPEAN JOURNAL OF CANCER
发表日期: 2014-09-01
DOI: 10.1016/j.ejca.2014.05.017
卷: 50, 期:13, 页:2251-2262
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: SWI/SNF COMPLEX ; CYTOPLASMIC P21 ; EXPRESSION ; GEMCITABINE ; RESISTANCE ; LINES ; SENSITIVITY ; EMT
英文摘要:

Gemcitabine is a standard chemotherapeutic agent for locally advanced and metastatic pancreatic cancer. However, the chemoresistance of pancreatic cancer is the major barrier to efficient chemotherapy. Here, we reported that BRG1, a chromatin modulator, was exclusively overexpressed in human pancreatic ductal adenocarcinoma tissues. BRG1 knockdown inhibited PANC-1 and MIA PaCa-2 cell growth in vitro and in vivo, reduced the phosphorylation/activation of Akt and p21(cip/waf), enhanced intrinsic and gemcitabine induced apoptosis and attenuated gemcitabine-induced downregulation of E-cadherin. Moreover, by establishing acquired chemoresistance of MIA PaCa-2 cells in vitro, we found that BRG1 knockdown effectively reversed the chemoresistance to gemcitabine. Surprisingly, inhibiting Akt phosphorylation resulted in BRG1 suppression in pancreatic cancer cells, indicating BRG1 as a new downstream target of Akt signalling. Taken together, our findings suggest that BRG1 promotes both intrinsic and acquired chemoresistance of pancreatic cancer cells, and BRG1 crosstalks with Akt signalling to form a positive feedback loop to promote pancreatic cancer development. (C) 2014 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81172184 ; 81372605 ; 7122188
项目资助者: The National Natural Science Foundation of China ; Beijing Natural Science Foundation
WOS记录号: WOS:000340849800008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57210
Appears in Collections:北京大学第一临床医学院_普通外科_期刊论文

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作者单位: 1.Peking Univ First Hosp, Dept Gen Surg, Beijing 100034, Peoples R China
2.Univ Ulm, Clin Gen Visceral & Transplantat Surg, D-89069 Ulm, Germany

Recommended Citation:
Liu, Xiaoran,Tian, Xiaodong,Wang, Feng,et al. BRG1 promotes chemoresistance of pancreatic cancer cells through crosstalking with Akt signalling[J]. EUROPEAN JOURNAL OF CANCER,2014,50(13):2251-2262.
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