Molecular players and cellular pathways in Estrogen-modulated breast cancer

Emily Powell, Wen Xie, Wei Xu

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Estrogens have been the most implicated etiological factor for breast cancer. The biological actions of estrogens are transduced by their binding to two estrogen receptors (ERs), ERα and ERβ, which are hormone-dependent transcription factors. These receptors translate the estrogenic signal into a physiological response by four distinct pathways. In the classical pathway, estrogen binding to ERα or ERβ leads to the formation of each respective homodimer or ERα/β heterodimers; the dimer pair induced defines the resulting cellular physiological response, as ERα and ERβ have opposing roles in regulating estrogen action: ERα promotes while ERβ inhibits estrogen-dependent cell growth. These dimers then directly bind to specific DNA sequences in the promoter regions of target genes to control transcription. Estrogens may also activate "tethering" pathways via ERα or ERβ, in which ERs directly interact with other transcription factors which recognize and bind DNA; as players in these tethering pathways, ERs do not directly bind to DNA. Growth factors may also activate ERs by activation of signaling cascades resulting in the phosphorylation of specific residues on ERs, leading to their activation; in this pathway, direct binding of estrogenic ligands to ERs is not required for their transcriptional activation. The fourth and perhaps most controversial mechanism of ER activation is by a subpopulation of ERs which localize to the cellular membrane and initiate rapid extra-nuclear signaling cascades. Because ERs are central hubs for the physiological response to estrogens in breast cancer, a concerted effort has been dedicated to targeting these receptors for the treatment of this deadly disease. This chapter will focus on various molecular pathways exerted by ERα and ERβ and their potential implications in future breast cancer therapeutics.

Original languageEnglish (US)
Title of host publicationFemale Sex Hormones and Cancers
PublisherNova Science Publishers, Inc.
Pages25-62
Number of pages38
ISBN (Print)9781617286964
StatePublished - 2012

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine

Fingerprint

Dive into the research topics of 'Molecular players and cellular pathways in Estrogen-modulated breast cancer'. Together they form a unique fingerprint.

Cite this