Transcriptional regulation of the transforming growth factor-beta2 gene in glioblastoma cells

In Vitro Cell Dev Biol Anim. Nov-Dec 2001;37(10):684-90. doi: 10.1290/1071-2690(2001)037<0684:TROTTG>2.0.CO;2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activating Transcription Factor 1
  • Binding Sites
  • Blotting, Western / methods
  • DNA-Binding Proteins*
  • Gene Expression Regulation*
  • Glioblastoma
  • Humans
  • Phosphorylation
  • Promoter Regions, Genetic
  • Serine / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta2
  • Tumor Cells, Cultured
  • Upstream Stimulatory Factors

Substances

  • Activating Transcription Factor 1
  • DNA-Binding Proteins
  • TGFB2 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • USF1 protein, human
  • USF2 protein, human
  • Upstream Stimulatory Factors
  • Serine