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Mutations in the estrogen receptor gene

M Sluyser1

  • 1Department of Tumor Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Human Mutation
|January 1, 1995
PubMed

Insights

Mutations in the estrogen receptor (ER) create abnormal forms that can drive cancer growth without estrogen and cause resistance to endocrine therapy. These ER variants are found in breast cancer and meningiomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Estrogen receptor (ER) mutations are implicated in various cancers.
  • Aberrant splicing of ER mRNA leads to altered protein forms.

Purpose of the Study:

  • To investigate the functional consequences of somatically generated ER variants.
  • To understand the role of ER variants in endocrine therapy resistance in breast cancer.
  • To explore the presence of ER variants in other tumor types, such as meningiomas.

Main Methods:

  • Analysis of mRNA/cDNA from breast cancer biopsies and cell lines.
  • Functional studies of ER variants in expression systems.

Main Results:

  • Identified truncated or internally deleted ER protein forms due to aberrant splicing.
  • Demonstrated dominant-positive ER variants active without estrogen.
  • Showcased dominant-negative ER variants inhibiting normal receptor function.
  • Observed similar abnormally spliced ER forms in human meningiomas.

Conclusions:

  • ER variants can confer dominant-positive or dominant-negative functions.
  • These ER variants are implicated in endocrine therapy resistance in breast cancer.
  • Abnormally spliced ER forms are present in both breast cancer and meningiomas.

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