Estrogen suppresses HOXB2 expression via ERα in breast cancer cells

Ajay Kumar1, Arun Dhillon1, Mohan Chowdenahalli Manjegowda1

  • 1Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.

Gene
|June 1, 2021
PubMed

Insights

Estrogen suppresses the tumor suppressor HOXB2 in breast cancer. This study reveals estrogen receptor alpha (ERα) mediates this suppression, impacting HOXB2

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • HOXB2, a homeobox transcription factor, exhibits altered expression in various solid tumors.
  • HOXB2 has been identified as a tumor suppressor in breast cancer, but its mechanism remains unclear.
  • Estrogen-regulated gene expression and HOX gene networks are implicated in breast cancer pathophysiology.

Purpose of the Study:

  • To investigate the relationship between estrogen signaling and HOXB2 expression in breast cancer.
  • To elucidate the molecular mechanisms underlying estrogen's effect on HOXB2.

Main Methods:

  • Utilized a mouse model and human breast cancer cell lines (MCF-7, T47D).
  • Employed an estrogen receptor alpha (ERα) agonist (PPT) and siRNA-mediated ERα knockdown.
  • Performed in-silico promoter analysis for Estrogen Response Elements (EREs) and chromatin immunoprecipitation (ChIP) assays.

Main Results:

  • Estrogen was found to suppress HOXB2 expression in both mouse models and human cell lines.
  • ERα activation by PPT led to HOXB2 suppression, confirmed by ERα knockdown.
  • ERα binds to EREs in the HOXB2 promoter region upon estrogen stimulation.

Conclusions:

  • Estrogen signaling, primarily through ERα, actively suppresses HOXB2 expression in breast cancer.
  • This estrogen-mediated suppression of a tumor suppressor warrants further investigation into its role in breast cancer progression.
  • Understanding this interaction is crucial for developing targeted breast cancer therapies.

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