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Title: PTEN enhances TNF-induced apoptosis through modulation of nuclear factor-{kappa}B signaling pathway in human glioma cells

The PTEN tumor suppressor gene modulates cell growth and survival known to be regulated by the activation of the transcription factor NF{kappa}B, suggesting PTEN might affect the NF{kappa}B activation pathway. We found that PTEN inhibited NF{kappa}B activation induced by TNF. The suppression of NF{kappa}B activation correlated with sequential inhibition of the tumor necrosis factor-induced expression of NF{kappa}B-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin) gene products. Downregulation of the antiapoptotic genes by PTEN increased TNF-induced apoptosis, as indicated by caspase activation, TUNEL, annexin staining, and esterase assay. We conclude that the ectopic expression of PTEN enhances TNF-induced apoptosis and downregulates the proliferation of glioma cells through the suppression of various molecules including NF{kappa}B, and various mediators of cellular survival and proliferation, and that this targets might be essential for its central role in the growth and survival of glioma cancer cells.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [3]
  1. Brain Tumor Center, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (United States). E-mail: Dkoul@mdnderson.org
  2. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (United States)
  3. Brain Tumor Center, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (United States)
Publication Date:
OSTI Identifier:
20854574
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 350; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2006.09.077; PII: S0006-291X(06)02109-7; Copyright (c) 2006 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; APOPTOSIS; BORON CHLORIDES; CELL PROLIFERATION; GENES; GLIOMAS; INHIBITION; MODULATION; TRANSCRIPTION FACTORS