Role of specificity protein transcription factors in estrogen-induced gene expression in MCF-7 breast cancer cells

Shaheen Khan, Fei Wu, Shengxi Liu, Qian Wu, Stephen Safe

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Deletion analysis of several 17β-estradiol (E2)-responsive genes have identified GC-rich sites that are associated with hormone-induced transactivation in MCF-7 breast cancer cells. However, the role of individual specificity proteins (Sps) in mediating hormone-induced gene expression has not been unequivocally determined. In transient transfection studies using E2-responsive GC-rich promoters from the E2F1, carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD), and retinoic acid receptor α (RARα) genes, RNA interference using small inhibitory RNAs for Sp1 (iSp1), Sp3 (iSp3), and Sp4 (iSp4) decreased both basal and E2-induced transactivation. The contributions of individual Sp proteins to basal and E2-induced activity were promoter dependent, iSp1, iSp3, and iSp4 also significantly inhibited hormonal induction of E2F1, CAD, and RARα mRNA levels; however, the enhanced inhibitory effects of the latter two small inhibitory RNAs suggest that Sp3 and Sp4 play a major role in estrogen receptor α/Sp-mediated gene expression in MCF-7 cells.

Original languageEnglish (US)
Pages (from-to)289-304
Number of pages16
JournalJournal of molecular endocrinology
Volume39
Issue number3-4
DOIs
StatePublished - Sep 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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