Transcriptional regulation of the transforming growth factor-β2 gene in glioblastoma cells

M. Kingsley-Kallesen, T. A. Luster, A Angie Rizzino

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The expression of transforming growth factor-β2 (TGF-β2) appears to play a strong role in the establishment and progression of glial tumors. In particular, elevated expression of TGF-β2 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-β2 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-β2 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-β2 activity by 80-95% in glioblastoma cells. We conclude that the binding of transcription factors, in particular the USF proteins, to the TGF-β2 promoter is essential for its expression and possibly its up-regulation in glioblastomas.

Original languageEnglish (US)
Pages (from-to)684-690
Number of pages7
JournalIn Vitro Cellular and Developmental Biology - Animal
Volume37
Issue number10
Publication statusPublished - Dec 1 2001

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Keywords

  • ATF-1
  • CRE/ATF
  • CREB
  • E-box
  • U87MG
  • USF

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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