Sp3 Is a Transcriptional Repressor of Transforming Growth Factor-β Receptors

Sudhakar Ammanamanchi, Michael G. Brattain

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

MCF-7E breast cancer cells express transforming growth factor-β (TGF-β) receptors RI and RII in comparison to MCF-7L cells. We present data showing that Sp3 acts as a transcriptional repressor of RI and RII in MCF-7L cells and GEO colon cancer cells. MCF-7L and GEO cells express high levels of Sp3 protein. Gel shift analysis indicated enhanced binding of Sp3 from MCF-7L cells to a consensus Sp1 oligonucleotide. South-western data indicated increased binding of Sp3 to RI and RII promoters in MCF-7L cells, suggesting a correlation between Sp3 binding and reduced expression of TGF-β receptors in MCF-7L cells. Cotransfection of CMV-Sp3 cDNA with RI and RII promoter-luciferase reporter constructs decreased RI and RII promoter activities by 70% in MCF-7E and GEO cells. Southwestern analysis detected the binding of transiently expressed Sp3 to RI and RII promoters in MCF-7E cells. Significantly, ectopic Sp3 expression led to repression of RI and RII transcripts in MCF-7E cells. This report demonstrates that inappropriate overexpression of Sp3 is a mechanism that contributes to repression of TGF-β receptors.

Original languageEnglish (US)
Pages (from-to)3348-3352
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number5
DOIs
StatePublished - Feb 2 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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