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A pivotal role for HOXB7 protein in endocrine resistant breast cancer

Kideok Jin1, Saraswati Sukumar1

  • 1Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Oncoscience
|December 24, 2015
PubMed

Insights

HOXB7 overexpression drives tamoxifen resistance in breast cancer by activating receptor tyrosine kinase pathways. Targeting HOXB7 and its regulators may restore tamoxifen sensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tamoxifen resistance is a major challenge in breast cancer treatment.
  • The transcription factor HOXB7 is implicated in tamoxifen-resistant breast cancer.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which HOXB7 promotes tamoxifen resistance.
  • To identify potential therapeutic targets for overcoming tamoxifen resistance.

Main Methods:

  • Investigated HOXB7's role in regulating receptor tyrosine kinase (RTK) pathways.
  • Analyzed the interplay between HOXB7, ERα, HER2, MYC, and miR-196a.
  • Examined the direct binding of HOXB7 to the EGFR promoter.

Main Results:

  • HOXB7 overexpression upregulates EGFR via direct promoter binding.
  • HOXB7, as a cofactor with ERα, overexpresses HER2 and other ER-target genes.
  • A feedback loop involving HER2, MYC, and miR-196a regulates HOXB7 expression.

Conclusions:

  • HOXB7 drives tamoxifen resistance through RTK pathway activation and a novel regulatory loop.
  • This study identifies HOXB7, EGFR, HER2, MYC, and miR-196a as potential therapeutic targets.
Keywords:
ERHOXB7MYCbreast cancertamoxifen-resistance

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