Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) α or ERβ in human osteosarcoma cells: Distinct and common target genes for these receptors

Fabio Stossi, Daniel H. Barnett, Jonna Frasor, Barry Komm, C. Richard Lyttle, Benita S Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors α and β (ERα and ERβ). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERα or ERβ, at levels comparable with those in osteoblasts, and we characterized their response to 17β-estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the approximately 100 regulated genes we identified, some were stimulated by E2 equally through ERα and ERβ, whereas others were selectively stimulated via ERa or ERβ. The E2-regulated genes showed three distinct temporal patterns of expression over the 48-h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERβ, in keeping with the selective E2 enhancement of the motility of ERβ-containing cells. On genes regulated equally by E2 via ERα or ERβ, the phytoestrogen genistein preferentially stimulated gene expression via ERβ. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation.

Original languageEnglish (US)
Pages (from-to)3473-3486
Number of pages14
JournalEndocrinology
Volume145
Issue number7
DOIs
StatePublished - Jul 1 2004

Fingerprint

Osteosarcoma
Estrogen Receptors
Estrogens
Gene Expression
Genes
Osteoblasts
Cell Movement
Phytoestrogens
Genistein
Cytoskeleton
Estradiol
Signal Transduction
Cytokines

ASJC Scopus subject areas

  • Endocrinology

Cite this

Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) α or ERβ in human osteosarcoma cells : Distinct and common target genes for these receptors. / Stossi, Fabio; Barnett, Daniel H.; Frasor, Jonna; Komm, Barry; Lyttle, C. Richard; Katzenellenbogen, Benita S.

In: Endocrinology, Vol. 145, No. 7, 01.07.2004, p. 3473-3486.

Research output: Contribution to journalArticle

@article{2ef967e76ad949b09d33bc9be8777f31,
title = "Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) α or ERβ in human osteosarcoma cells: Distinct and common target genes for these receptors",
abstract = "Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors α and β (ERα and ERβ). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERα or ERβ, at levels comparable with those in osteoblasts, and we characterized their response to 17β-estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the approximately 100 regulated genes we identified, some were stimulated by E2 equally through ERα and ERβ, whereas others were selectively stimulated via ERa or ERβ. The E2-regulated genes showed three distinct temporal patterns of expression over the 48-h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERβ, in keeping with the selective E2 enhancement of the motility of ERβ-containing cells. On genes regulated equally by E2 via ERα or ERβ, the phytoestrogen genistein preferentially stimulated gene expression via ERβ. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation.",
author = "Fabio Stossi and Barnett, {Daniel H.} and Jonna Frasor and Barry Komm and Lyttle, {C. Richard} and Katzenellenbogen, {Benita S}",
year = "2004",
month = "7",
day = "1",
doi = "10.1210/en.2003-1682",
language = "English (US)",
volume = "145",
pages = "3473--3486",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "7",

}

TY - JOUR

T1 - Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) α or ERβ in human osteosarcoma cells

T2 - Distinct and common target genes for these receptors

AU - Stossi, Fabio

AU - Barnett, Daniel H.

AU - Frasor, Jonna

AU - Komm, Barry

AU - Lyttle, C. Richard

AU - Katzenellenbogen, Benita S

PY - 2004/7/1

Y1 - 2004/7/1

N2 - Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors α and β (ERα and ERβ). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERα or ERβ, at levels comparable with those in osteoblasts, and we characterized their response to 17β-estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the approximately 100 regulated genes we identified, some were stimulated by E2 equally through ERα and ERβ, whereas others were selectively stimulated via ERa or ERβ. The E2-regulated genes showed three distinct temporal patterns of expression over the 48-h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERβ, in keeping with the selective E2 enhancement of the motility of ERβ-containing cells. On genes regulated equally by E2 via ERα or ERβ, the phytoestrogen genistein preferentially stimulated gene expression via ERβ. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation.

AB - Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors α and β (ERα and ERβ). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERα or ERβ, at levels comparable with those in osteoblasts, and we characterized their response to 17β-estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the approximately 100 regulated genes we identified, some were stimulated by E2 equally through ERα and ERβ, whereas others were selectively stimulated via ERa or ERβ. The E2-regulated genes showed three distinct temporal patterns of expression over the 48-h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERβ, in keeping with the selective E2 enhancement of the motility of ERβ-containing cells. On genes regulated equally by E2 via ERα or ERβ, the phytoestrogen genistein preferentially stimulated gene expression via ERβ. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation.

UR - http://www.scopus.com/inward/record.url?scp=3042681155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042681155&partnerID=8YFLogxK

U2 - 10.1210/en.2003-1682

DO - 10.1210/en.2003-1682

M3 - Article

C2 - 15033914

AN - SCOPUS:3042681155

VL - 145

SP - 3473

EP - 3486

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 7

ER -