Estrogen receptor mutations in human disease

Endocr Rev. 2004 Dec;25(6):869-98. doi: 10.1210/er.2003-0010.


As early as the 1800s, the actions of estrogen have been implicated in the development and progression of breast cancer. The estrogen receptor (ER) was identified in the late 1950s and purified a few years later. However, it was not until the 1980s that the first ER was molecularly cloned, and in the mid 1990s, a second ER was cloned. These two related receptors are now called ERalpha and ERbeta, respectively. Since their discovery, much research has focused on identifying alterations within the coding sequence of these receptors in clinical samples. As a result, a large number of naturally occurring splice variants of both ERalpha and ERbeta have been identified in normal epithelium and diseased or cancerous tissues. In contrast, only a few point mutations have been identified in human patient samples from a variety of disease states, including breast cancer, endometrial cancer, and psychiatric diseases. To elucidate the mechanism of action for these variant isoforms or mutant receptors, experimental mutagenesis has been used to analyze the function of distinct amino acid residues in the ERs. This review will focus on ERalpha and ERbeta alterations in breast cancer.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Disease*
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / physiology
  • Estrogen Receptor beta / chemistry
  • Estrogen Receptor beta / genetics*
  • Estrogen Receptor beta / physiology
  • Exons / genetics
  • Humans
  • Mutation*
  • Point Mutation
  • RNA Splicing / genetics
  • RNA, Messenger / genetics


  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • RNA, Messenger