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

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