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Sp3 is a transcriptional repressor of transforming growth factor-beta receptors

S Ammanamanchi1, M G Brattain

  • 1Department of Surgery, University of Texas Health Science Center, San Antonio, Texas 78229, USA.

The Journal of Biological Chemistry
|October 12, 2000
PubMed

Insights

High Sp3 protein levels repress transforming growth factor-beta (TGF-beta) receptors RI and RII in cancer cells. This study reveals Sp3 overexpression as a mechanism contributing to TGF-beta receptor repression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • MCF-7E breast cancer cells express TGF-beta receptors RI and RII, unlike MCF-7L cells.
  • MCF-7L and GEO colon cancer cells exhibit high Sp3 protein levels.

Purpose of the Study:

  • To investigate the role of Sp3 in regulating TGF-beta receptor expression in cancer cells.
  • To determine if Sp3 acts as a transcriptional repressor of TGF-beta receptors RI and RII.

Main Methods:

  • Gel shift and Southwestern analyses to assess Sp3 binding to DNA and promoters.
  • Reporter gene assays (luciferase) to measure promoter activity.
  • Analysis of TGF-beta receptor transcript levels following Sp3 expression.

Main Results:

  • Sp3 protein from MCF-7L cells showed enhanced binding to Sp1 oligonucleotides and RI/RII promoters.
  • Overexpression of Sp3 significantly decreased RI and RII promoter activity by 70% in MCF-7E and GEO cells.
  • Ectopic Sp3 expression led to repression of RI and RII transcripts in MCF-7E cells.

Conclusions:

  • Sp3 functions as a transcriptional repressor of TGF-beta receptors RI and RII.
  • Inappropriate Sp3 overexpression is a mechanism contributing to the repression of TGF-beta receptors in cancer.

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