Estrogen receptor alpha and estrogen receptor beta: Regulation by selective estrogen receptor modulators and importance in breast cancer

B. S. Katzenellenbogen, J. A. Katzenellenbogen

Research output: Contribution to journalReview article

Abstract

Estrogens display intriguing tissue-selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer, for menopausal hormone replacement, and for fertility regulation. Certain compounds that act through the estrogen receptor (ER), now referred to as selective estrogen receptor modulators (SERMs), can demonstrate remarkable differences in activity in the various estrogen target tissues, functioning as agonists in some tissues but as antagonists in others. Recent advances elucidating the tripartite nature of the biochemical and molecular actions of estrogens provide a good basis for understanding these tissue-selective actions. As discussed in this thematic review, the development of optimal SERMs should now be viewed in the context of two estrogen receptor subtypes, ERα and ERβ, that have differing affinities and responsiveness to various SERMs, and differing tissue distribution and effectiveness at various gene regulatory sites. Cellular, biochemical, and structural approaches have also shown that the nature of the ligand affects the conformation assumed by the ER-ligand complex, thereby regulating its state of phosphorylation and the recruitment of different coregulator proteins. Growth factors and protein kinases that control the phosphorylation state of the complex also regulate the bioactivity of the ER. These interactions and changes determine the magnitude of the transcriptional response and the potency of different SERMs. As these critical components are becoming increasingly well defined, they provide a sound basis for the development of novel SERMs with optimal profiles of tissue selectivity as medical therapeutic agents.

Original languageEnglish (US)
Pages (from-to)335-344
Number of pages10
JournalBreast Cancer Research
Volume2
Issue number5
DOIs
StatePublished - Dec 1 2000

Fingerprint

Selective Estrogen Receptor Modulators
Estrogen Receptor beta
Estrogen Receptor alpha
Estrogen Receptors
Breast Neoplasms
Estrogens
Phosphorylation
Ligands
Tissue Distribution
Regulator Genes
Protein Kinases
Fertility
Intercellular Signaling Peptides and Proteins
Hormones
Therapeutics
Proteins

Keywords

  • Coactivators
  • Corepressors
  • Estrogen receptor
  • Ligands for estrogen receptors
  • Selective estrogen receptor modulators

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Estrogen receptor alpha and estrogen receptor beta : Regulation by selective estrogen receptor modulators and importance in breast cancer. / Katzenellenbogen, B. S.; Katzenellenbogen, J. A.

In: Breast Cancer Research, Vol. 2, No. 5, 01.12.2000, p. 335-344.

Research output: Contribution to journalReview article

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