Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Endocrinol. 2005 Jun;19(6):1555-68. Epub 2005 Mar 31.

Estrogen receptor alpha and beta heterodimers exert unique effects on estrogen- and tamoxifen-dependent gene expression in human U2OS osteosarcoma cells.

Author information

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 1601C Guggenheim, 200 1st Street Southwest, Rochester, Minnesota 55905, USA. Monroe.David@mayo.edu

Abstract

The 17beta-estradiol (E2) receptor isoforms [estrogen receptor (ER) alpha and ERbeta] bind E2 and selective ER modulators (SERMs) as homodimers (alpha/alpha or beta/beta) or heterodimers (alpha/beta) 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 ERalpha/beta heterodimer. This paper describes the development of a U2OS human osteosarcoma (osteoblast) cell line stably expressing both ERalpha and ERbeta 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-ERalpha/beta 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, retinoblastoma binding protein 1 and 7-dehydrocholesterol reductase, were found to contain estrogen response element-like sequences that directly bind the ERalpha/beta heterodimer. These results suggest that the expression of both ER isoforms, forming functional ERalpha/beta heterodimers, result in unique patterns of gene regulation, many of which are distinct from the genes regulated by the ER homodimers.

PMID:
15802376
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Atypon
    Loading ...
    Write to the Help Desk