Genomic Antagonism between Retinoic Acid and Estrogen Signaling in Breast Cancer

Sujun Hua, Ralf Kittler, Kevin P. White

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

Retinoic acid (RA) triggers antiproliferative effects in tumor cells, and therefore RA and its synthetic analogs have great potential as anticarcinogenic agents. Retinoic acid receptors (RARs) mediate RA effects by directly regulating gene expression. To define the genetic network regulated by RARs in breast cancer, we identified RAR genomic targets using chromatin immunoprecipitation and expression analysis. We found that RAR binding throughout the genome is highly coincident with estrogen receptor α (ERα) binding, resulting in a widespread crosstalk of RA and estrogen signaling to antagonistically regulate breast cancer-associated genes. ERα- and RAR-binding sites appear to be coevolved on a large scale throughout the human genome, often resulting in competitive binding activity at nearby or overlapping cis-regulatory elements. The highly coordinated intersection between these two critical nuclear hormone receptor signaling pathways provides a global mechanism for balancing gene expression output via local regulatory interactions dispersed throughout the genome.

Original languageEnglish (US)
Pages (from-to)1259-1271
Number of pages13
JournalCell
Volume137
Issue number7
DOIs
StatePublished - Jun 26 2009

Fingerprint

Retinoic Acid Receptors
Tretinoin
Estrogens
Breast Neoplasms
Genes
Gene expression
Estrogen Receptors
Genome
Anticarcinogenic Agents
Gene Expression
Competitive Binding
Chromatin Immunoprecipitation
Neoplasm Genes
Human Genome
Cytoplasmic and Nuclear Receptors
Crosstalk
Chromatin
Binding Sites

Keywords

  • HUMDISEASE
  • PROTEINS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Genomic Antagonism between Retinoic Acid and Estrogen Signaling in Breast Cancer. / Hua, Sujun; Kittler, Ralf; White, Kevin P.

In: Cell, Vol. 137, No. 7, 26.06.2009, p. 1259-1271.

Research output: Contribution to journalArticle

Hua, Sujun ; Kittler, Ralf ; White, Kevin P. / Genomic Antagonism between Retinoic Acid and Estrogen Signaling in Breast Cancer. In: Cell. 2009 ; Vol. 137, No. 7. pp. 1259-1271.
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