Transcriptional activation of heat shock protein 27 gene expression by 17β-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists

W. Porter, F. Wang, R. Duan, C. Qin, E. Castro-Rivera, K. Kim, S. Safe

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Heat shock protein 27 (Hsp 27) is expressed in mammary tumors and may play a role in tumor growth and response to anti-neoplastic drug therapy. 17β-Estradiol (E2) induces Hsp 27 mRNA levels in MCF-7 human breast cancer cells, and we have investigated the comparative inhibitory mechanisms using the aryl hydrocarbon receptor (AhR) agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the direct-acting antiestrogen ICI 164,384. TCDD inhibited E2-induced Hsp 27 gene expression and analysis of the Hsp 27 gene promoter showed that the inhibitory response was associated with AhR interactions with a pentanucleotide motif at -3 to +2 in the promoter that corresponded to the core sequence of a dioxin responsive element. In contrast, ICI 164,384 induced Hsp 27 gene expression and reporter gene activity in MCF-7 cells and this represents one of the few examples of the estrogen receptor-α (ERα) agonist activity of the 'pure' antiestrogen ICI 164,384.

Original languageEnglish (US)
Pages (from-to)31-42
Number of pages12
JournalJournal of Molecular Endocrinology
Volume26
Issue number1
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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