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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

Unliganded estrogen receptor-beta regulation of genes is inhibited by tamoxifen

Nitzan Levy1, Sreenivasan Paruthiyil, Xiaoyue Zhao

  • 1Department of Obstetrics, Gynecology and Reproductive , University of California, San Francisco, CA, USA.

Molecular and Cellular Endocrinology
|September 12, 2009
PubMed

Insights

Tamoxifen may negatively impact ERbeta-expressing breast tumors by blocking unliganded estrogen receptor beta (ERbeta) gene regulation. This antagonism affects growth-inhibitory genes, suggesting a potential therapeutic limitation.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Tamoxifen is a widely used breast cancer therapy, but resistance and paradoxical growth stimulation occur.
  • Unliganded estrogen receptor beta (ERbeta) has been shown to inhibit ERalpha-mediated cell proliferation.
  • The interaction between tamoxifen, ERbeta, and gene regulation in breast cancer requires further elucidation.

Purpose of the Study:

  • To investigate the potential negative effects of tamoxifen on ERbeta-expressing breast cancer cells.
  • To determine how tamoxifen affects gene regulation mediated by unliganded ERbeta.
  • To explore the molecular mechanisms underlying tamoxifen's antagonism of unliganded ERbeta.

Main Methods:

  • Gene expression profiling of MCF-7 cells treated with unliganded ERbeta.
  • Utilizing doxycycline-inducible U2OS-ERbeta cells to study gene activation by unliganded ERbeta.
  • Analyzing the effect of tamoxifen on ERbeta-mediated gene upregulation and coactivator recruitment.

Main Results:

  • Unliganded ERbeta upregulated 196 genes in MCF-7 cells.
  • Tamoxifen significantly inhibited 73 of these upregulated genes, including growth-inhibitory genes.
  • Tamoxifen abolished doxycycline-induced activation of NKG2E, MSMB, and TUB3A genes and blocked ERbeta recruitment of SRC-2 to the NKG2E gene.

Conclusions:

  • Tamoxifen exhibits an antagonistic action on unliganded ERbeta.
  • This antagonism suggests tamoxifen may exert negative effects on ERbeta-expressing breast tumors.
  • Findings highlight the complex role of ERbeta in tamoxifen response and breast cancer progression.

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