Transcriptional regulation of the transforming growth factor-beta2 gene in glioblastoma cells.
The expression of transforming growth factor-beta2 (TGF-beta2) appears to play a strong role in the establishment and progression of glial tumors. In particular, elevated expression of TGF-beta2 appears to be responsible for the impaired cell-mediated immunity often observed in patients with a glioblastoma. This study examined the regulation of the TGF-beta2 at the transcriptional level in the U87MG glioblastoma cell line. We demonstrate that a cAMP response element/activating transcription factor (CRE/ATF) site and an E-box motif located just upstream of the transcription start site are essential for the transcription of the TGF-beta2 gene in U87MG cells. Gel mobility analysis determined that activating transcription factor-1, and possibly cAMP-responsive element binding protein, binds to the CRE/ATF site, and upsteam stimulatory factor (USF) 1 and USF2 bind to the E-box motif. Interestingly, expression of a dominant negative USF protein down-regulates TGF-beta2 activity by 80-95% in glioblastoma cells. We conclude that the binding of transcription factors, in particular the USF proteins, to the TGF-beta2 promoter is essential for its expression and possibly its up-regulation in glioblastomas.
Kingsley-Kallesen
M
M
Eppley Institute for Research in Cancer and Allied Diseases and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-6805, USA.
Luster
T A
TA
Rizzino
A
A
D051697:Activating Transcription Factor 1; D001665:Binding Sites; D015153:Blotting, Western / Q000379:methods; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D005909:Glioblastoma; D006801:Humans; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053781:Transforming Growth Factor beta2; D014407:Tumor Cells, Cultured; D051720:Upstream Stimulatory Factors
D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; C509041:TGFB2 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; C497181:USF1 protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D012694:Serine