Estrogen receptor α and β heterodimers exert unique effects on estrogen- and tamoxifen-dependent gene expression in human U2Os osteosarcoma cells

David G. Monroe, Frank J. Secreto, Malayannan Subramaniam, Barbara J. Getz, Sundeep Khosla, Thomas C. Spelsberg

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

The 17β-estradiol (E2) receptor isoforms [estrogen receptor (ER) α and ERβ] bind E2 and selective ER modulators (SERMs) as homodimers (α/α or β/β) or heterodimers (α/β) to regulate gene expression. Although recent studies have shown that ER homodimers regulate unique sets of E2-responsive genes, little information exists regarding the transcriptional actions of the ERα/β heterodimer. This paper describes the development of a U2OS human osteosarcoma (osteoblast) cell line stably expressing both ERα and ERβ isoforms at a ratio of 1:4, a ratio reported to exist in normal, mature osteoblast cells derived from cancellous bone. The regulation of endogenous genes by E2 and 4-hydroxy-tamoxifen were measured in these cells using gene microarrays and real-time RT-PCR. Both E2 and 4-hydroxy-tamoxifen were shown to regulate unique sets of endogenous genes in the U2OS-ERα/β heterodimer cell line (20% and 27% of total, respectively), compared with all the genes regulated in U2OS-ER homodimer cell lines. Furthermore, two novel E2-regulated genes, retino-blastoma binding protein 1 and 7-dehydrocholesterol reductase, were found to contain estrogen response element-like sequences that directly bind the ERα/β heterodimer. These results suggest that the expression of both ER isoforms, forming functional ERα/β heterodimers, result in unique patterns of gene regulation, many of which are distinct from the genes regulated by the ER homodimers.

Original languageEnglish (US)
Pages (from-to)1555-1568
Number of pages14
JournalMolecular Endocrinology
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Estrogen receptor α and β heterodimers exert unique effects on estrogen- and tamoxifen-dependent gene expression in human U2Os osteosarcoma cells'. Together they form a unique fingerprint.

  • Cite this