Repression of transforming growth factor-β receptor type I promoter expression by Sp1 deficiency

Sumudra Periyasamy, Sudhakar Ammanamanchi, Manoranjani P.M. Tillekeratne, Michael G. Brattain

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

In this report, we describe the mechanism of TGF-β receptor type I (RI) repression in the GEO human colon carcinoma cells. Treatment of GEO cells with the DNA methyltransferase inhibitor, 5 azacytidine induced RI expression and restored TGF-β response. A stably transfected RI promoter-reporter construct (RI-Luc) expressed higher activity in the 5 aza C treated GEO cells, suggesting the activation of a transactivator for RI transcription. Gel shift analysis indicated enhanced binding of proteins from the 5 aza C treated nuclear extracts to radiolabeled Sp1 oligonucleotides specifically contained in the RI promoter. Protein stability studies after cyclohexamide treatment suggested an increase in the Sp1 protein stability from the 5 aza C treated GEO cells. Further, transfection of Sp1 cDNA into untreated GEO control cells increased RI promoter activity and thus induced RI expression. 5 aza C mediated Sp1 expression in Sp1 deficient GEO colon and MCF-7 breast cancer cells also enhanced the activity of several other Sp1 dependent promoters such as TGF-β receptor type II (RII), Cyclin A and p21/waf1/cip1. These results indicate that restoration of Sp1 in several different types of Sp1 deficient cells leads to enhanced activation of a wide range of Sp1 dependent promoters.

Original languageEnglish (US)
Pages (from-to)4660-4667
Number of pages8
JournalOncogene
Volume19
Issue number40
DOIs
StatePublished - Sep 21 2000
Externally publishedYes

Keywords

  • Azacytidine
  • Transforming growth factor-β
  • Transforming growth factor-β receptor type I (RI)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Periyasamy, S., Ammanamanchi, S., Tillekeratne, M. P. M., & Brattain, M. G. (2000). Repression of transforming growth factor-β receptor type I promoter expression by Sp1 deficiency. Oncogene, 19(40), 4660-4667. https://doi.org/10.1038/sj.onc.1203822