Identification of an enhancer element in the estrogen receptor upstream region: Implications for regulation of ER transcription in breast cancer

Claudia S. Cohn, Julia Ann Sullivan, Todd Kiefer, Steven M. Hill

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The estrogen receptor (ER) serves as a diagnostic marker for the treatment of breast cancer. Patients with ER-positive breast tumors are likely to respond to hormonal therapies, while ER-negative breast cancers are resistant to endocrine therapies. Most ER-negative tumors do not express detectable levels of ER transcript, highlighting the importance of transcriptional regulation. A novel regulatory element which resembles a steroid hormone response element has been identified in the 5'-flanking region of the human ER gene. We observed 3- to 5-fold higher specific binding to this element in nuclear extracts from ER-expressing MCF-7 breast cancer cells compared to ER-negative MDA-MB-231 breast tumor cells. We termed the factor(s) which bind to this cis-element estrogen receptor upstream binding factor-1 (ERUBF-1). In transient transfection assays in MCF-7 cells, the ERUBF-1 binding site elicited a 20-fold increase in luciferase activity over the ER P1, promoter. This enhancer element was significantly more active in the ER-positive MCF-7 cell line compared to the ER-negative MDA-MB-231 cell line. These data indicate that ERUBF-1 plays an important role in the transcriptional regulation of the ER gene in breast cancer. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)25-36
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume158
Issue number1-2
DOIs
StatePublished - Dec 20 1999

Bibliographical note

Funding Information:
The authors would like to thank Dr Lin Yuan for her technical assistance and Dr Ron Weigel for his generous gift of the 40-210 construct. This work was supported by a grant from the American Cancer Society (BE72794) to SMH and by a National Research Service Award (F32CA68748) from the NIH to CSC.

Keywords

  • (MCF-7 breast cancer cells)
  • (MDA-MB-231 breast cancer cells)
  • Breast cancer
  • Enhancer
  • Estrogen receptor
  • Steroid receptors

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