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

  • Cell Growth/Differentiation/Apoptosis
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Summary

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 cellmediated 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.

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  1. Eppley Institute for Research in Cancer and Allied Diseases and Department of Pathology and Microbiology, University of Nebraska Medical Center, 68198-6805, Omaha, Nebraska

    Michelle Kingsley-Kallesen, Troy A. Luster & Angie Rizzino

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  1. Michelle Kingsley-Kallesen
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  2. Troy A. Luster
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  3. Angie Rizzino
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Correspondence to Angie Rizzino.

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Kingsley-Kallesen, M., Luster, T.A. & Rizzino, A. Transcriptional regulation of the transforming growth factor-β2 gene in glioblastoma cells. In Vitro Cell.Dev.Biol.-Animal 37, 684–690 (2001). https://doi.org/10.1290/1071-2690(2001)037<0684:TROTTG>2.0.CO;2

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  • DOI: https://doi.org/10.1290/1071-2690(2001)037<0684:TROTTG>2.0.CO;2

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