PTEN enhances TNF-induced apoptosis through modulation of nuclear factor-{kappa}B signaling pathway in human glioma cells
- Brain Tumor Center, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (United States)
- Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (United States)
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.
- OSTI ID:
- 20854574
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 350, 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); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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