PTEN enhances TNF-induced apoptosis through modulation of nuclear factor-kappaB 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 NFkappaB, suggesting PTEN might affect the NFkappaB activation pathway. We found that PTEN inhibited NFkappaB activation induced by TNF. The suppression of NFkappaB activation correlated with sequential inhibition of the tumor necrosis factor-induced expression of NFkappaB-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 NFkappaB, 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.
Koul
Dimpy
D
Brain Tumor Center, Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Dkoul@mdanderson.org
Takada
Yasunari
Y
Shen
Ruijun
R
Aggarwal
Bharat B
BB
Yung
W K Alfred
WK
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051059:PTEN Phosphohydrolase