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Title: RNA interference targeting raptor inhibits proliferation of gastric cancer cells

Abstract

Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G{sub 0}/G{sub 1}-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D{sub 3} and p21{sup Waf1}, which stabilizes cyclin D/cdk4 complex for G{sub 1}-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.

Authors:
;  [1];  [1];  [2];  [1];  [1];  [1]
  1. Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)
  2. (China)
Publication Date:
OSTI Identifier:
22212145
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 317; Journal Issue: 10; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOGENESIS; CELL CYCLE; CELL PROLIFERATION; NEOPLASMS; PROTEINS; RNA; THERAPY

Citation Formats

Wu, William Ka Kei, Lee, Chung Wa, Cho, Chi Hin, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, Chan, Francis Ka Leung, Yu, Jun, E-mail: junyu@cuhk.edu.hk, and Sung, Joseph Jao Yiu, E-mail: joesung@cuhk.edu.hk. RNA interference targeting raptor inhibits proliferation of gastric cancer cells. United States: N. p., 2011. Web. doi:10.1016/J.YEXCR.2011.03.005.
Wu, William Ka Kei, Lee, Chung Wa, Cho, Chi Hin, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, Chan, Francis Ka Leung, Yu, Jun, E-mail: junyu@cuhk.edu.hk, & Sung, Joseph Jao Yiu, E-mail: joesung@cuhk.edu.hk. RNA interference targeting raptor inhibits proliferation of gastric cancer cells. United States. doi:10.1016/J.YEXCR.2011.03.005.
Wu, William Ka Kei, Lee, Chung Wa, Cho, Chi Hin, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, Chan, Francis Ka Leung, Yu, Jun, E-mail: junyu@cuhk.edu.hk, and Sung, Joseph Jao Yiu, E-mail: joesung@cuhk.edu.hk. Fri . "RNA interference targeting raptor inhibits proliferation of gastric cancer cells". United States. doi:10.1016/J.YEXCR.2011.03.005.
@article{osti_22212145,
title = {RNA interference targeting raptor inhibits proliferation of gastric cancer cells},
author = {Wu, William Ka Kei and Lee, Chung Wa and Cho, Chi Hin and School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong and Chan, Francis Ka Leung and Yu, Jun, E-mail: junyu@cuhk.edu.hk and Sung, Joseph Jao Yiu, E-mail: joesung@cuhk.edu.hk},
abstractNote = {Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G{sub 0}/G{sub 1}-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D{sub 3} and p21{sup Waf1}, which stabilizes cyclin D/cdk4 complex for G{sub 1}-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.},
doi = {10.1016/J.YEXCR.2011.03.005},
journal = {Experimental Cell Research},
number = 10,
volume = 317,
place = {United States},
year = {Fri Jun 10 00:00:00 EDT 2011},
month = {Fri Jun 10 00:00:00 EDT 2011}
}
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