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A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions

Fuqua, S A ; Wiltschke, C ; Zhang, Q X ; Borg, A LU ; Castles, C G ; Friedrichs, W E ; Hopp, T ; Hilsenbeck, S ; Mohsin, S and O'Connell, P , et al. (2000) In Cancer Research 60(15). p.4026-4029
Abstract

The best current model of breast cancer evolution suggests that most cancers arise from certain premalignant lesions. We have identified a common (34%) somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59 typical hyperplasias, a type of early premalignant breast lesion. The mutation, which affects the border of the hinge and hormone binding domains of ER-alpha, showed increased sensitivity to estrogen as compared with wild-type ER-alpha in stably transfected breast cancer cells, including markedly increased proliferation at subphysiological levels of estrogen. The mutated ER-alpha exhibits enhanced binding to the TIF-2 coactivator at low levels of hormone, which may partially explain its increased estrogen... (More)

The best current model of breast cancer evolution suggests that most cancers arise from certain premalignant lesions. We have identified a common (34%) somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59 typical hyperplasias, a type of early premalignant breast lesion. The mutation, which affects the border of the hinge and hormone binding domains of ER-alpha, showed increased sensitivity to estrogen as compared with wild-type ER-alpha in stably transfected breast cancer cells, including markedly increased proliferation at subphysiological levels of estrogen. The mutated ER-alpha exhibits enhanced binding to the TIF-2 coactivator at low levels of hormone, which may partially explain its increased estrogen responsiveness. These data suggest that this mutation may promote or accelerate the development of cancer from premalignant breast lesions.

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publication status
published
subject
keywords
Breast/pathology, Breast Neoplasms/genetics, Cell Division/drug effects, DNA/analysis, DNA, Neoplasm/analysis, Dose-Response Relationship, Drug, Estradiol/pharmacology, Estrogen Receptor alpha, Humans, Hyperplasia/genetics, Mutation, Precancerous Conditions/genetics, Receptors, Estrogen/drug effects, Reverse Transcriptase Polymerase Chain Reaction, Transfection
in
Cancer Research
volume
60
issue
15
pages
4026 - 4029
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:10945602
  • scopus:0033898141
ISSN
0008-5472
language
English
LU publication?
yes
id
1bc892f5-21c5-41ad-ac99-1763a3e784df
alternative location
https://cancerres.aacrjournals.org/content/60/15/4026.long
date added to LUP
2019-05-27 22:55:38
date last changed
2021-09-12 03:13:04
@article{1bc892f5-21c5-41ad-ac99-1763a3e784df,
  abstract     = {<p>The best current model of breast cancer evolution suggests that most cancers arise from certain premalignant lesions. We have identified a common (34%) somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59 typical hyperplasias, a type of early premalignant breast lesion. The mutation, which affects the border of the hinge and hormone binding domains of ER-alpha, showed increased sensitivity to estrogen as compared with wild-type ER-alpha in stably transfected breast cancer cells, including markedly increased proliferation at subphysiological levels of estrogen. The mutated ER-alpha exhibits enhanced binding to the TIF-2 coactivator at low levels of hormone, which may partially explain its increased estrogen responsiveness. These data suggest that this mutation may promote or accelerate the development of cancer from premalignant breast lesions.</p>},
  author       = {Fuqua, S A and Wiltschke, C and Zhang, Q X and Borg, A and Castles, C G and Friedrichs, W E and Hopp, T and Hilsenbeck, S and Mohsin, S and O'Connell, P and Allred, D C},
  issn         = {0008-5472},
  language     = {eng},
  number       = {15},
  pages        = {4026--4029},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions},
  url          = {https://cancerres.aacrjournals.org/content/60/15/4026.long},
  volume       = {60},
  year         = {2000},
}