Regulation of the estrogen-responsive pS2 gene in MCF-7 human breast cancer cells

Jongsook Kim, Larry N. Petz, Yvonne S. Ziegler, Jennifer R. Wood, Sara J. Potthoff, Ann M. Nardulli

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

To understand how hormones and antihormones regulate transcription of estrogen-responsive genes, in vivo footprinting was used to examine the endogenous pS2 gene in MCF-7 cells. While the consensus pS2 estrogen response element (ERE) half site was protected in the absence of hormone, both the consensus and imperfect ERE half sites were protected in the presence of estrogen. 4-Hydroxytamoxifen and ICI 182,780 elicited distinct footprinting patterns, which differed from those observed with vehicle- or with estrogen-treated cells suggesting that the partial agonist/antagonist and antagonist properties of 4-hydroxytamoxifen or ICI 182,780, respectively, may be partially explained by modulation of protein-DNA interactions. Footprinting patterns in and around the TATA and CAAT sequences were identical in the presence and in the absence of estrogen suggesting that the basal promoter is accessible and poised for transcription even in the absence of hormone. In vitro DNase I footprinting experiments demonstrated that the estrogen receptor bound to the pS2 ERE and that adjacent nucleotides were protected by MCF-7 nuclear proteins. These findings indicate that transcription of the pS2 gene is modulated by alterations in protein binding to multiple sites upstream of the basal promoter, but not by changes in protein-DNA interactions in the basal promoter.

Original languageEnglish (US)
Pages (from-to)157-168
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume74
Issue number4
DOIs
StatePublished - Nov 15 2000

Fingerprint

Estrogens
Genes
Cells
Breast Neoplasms
Response Elements
Transcription
Hormones
Deoxyribonuclease I
DNA
MCF-7 Cells
Nuclear Proteins
Protein Binding
Estrogen Receptors
Proteins
Nucleotides
Modulation
Experiments
fulvestrant
afimoxifene

Keywords

  • Antiestrogen
  • Chromatin
  • Estrogen
  • Transcription

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Regulation of the estrogen-responsive pS2 gene in MCF-7 human breast cancer cells. / Kim, Jongsook; Petz, Larry N.; Ziegler, Yvonne S.; Wood, Jennifer R.; Potthoff, Sara J.; Nardulli, Ann M.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 74, No. 4, 15.11.2000, p. 157-168.

Research output: Contribution to journalArticle

Kim, Jongsook ; Petz, Larry N. ; Ziegler, Yvonne S. ; Wood, Jennifer R. ; Potthoff, Sara J. ; Nardulli, Ann M. / Regulation of the estrogen-responsive pS2 gene in MCF-7 human breast cancer cells. In: Journal of Steroid Biochemistry and Molecular Biology. 2000 ; Vol. 74, No. 4. pp. 157-168.
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