Transcriptional activation of cathepsin D gene expression by 17β-estradiol: Mechanism of aryl hydrocarbon receptor-mediated inhibition

Fan Wang, Ismael Samudio, Stephen Safe

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

17β-estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast cancer cells and this response is inhibited by aryl hydrocarbon receptor (AhR) agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Analysis of the cathepsin D gene promoter initially identified a pentanucleotide GCGTG core dioxin responsive element (DRE) that blocked E2 action by inhibiting formation of a transcriptionally active estrogen receptor (ER)-Sp1 complex. A second functional downstream inhibitory DRE (iDRE2) (-130 to -126) has now been identified in the cathepsin D gene promoter and inhibition of E2-induced transactivation involves inhibitory AhR crosstalk with the E2-responsive adenovirus major late promoter element (MLPE) at -124 to -104 in the cathepsin D gene promoter. The MLPE site primarily binds USF1/USF2 and ERα, and gel mobility shift and DNA footprinting assays show that the AhR complex decreases binding of these transcription factors to the MLPE.

Original languageEnglish (US)
Pages (from-to)91-103
Number of pages13
JournalMolecular and cellular endocrinology
Volume172
Issue number1-2
DOIs
StatePublished - Feb 14 2001

Keywords

  • Ah receptor
  • Cathepsin D
  • ER
  • Inhibitory crosstalk

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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