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Estrogen receptor-beta is a potential target for triple negative breast cancer treatment

David Austin1, Nalo Hamilton2, Yahya Elshimali1

  • 1Department of Medicine, Division of Cancer Research and Training, Charles Drew University School of Medicine and Science, Los Angeles, CA 90059, USA.

Oncotarget
|October 20, 2018
PubMed

Insights

Estrogen receptor-beta (ERβ) and IGF2 are key drivers in triple-negative breast cancer (TNBC) pathogenesis, particularly in African American patients. Targeting the IGF2/ERβ axis offers a promising therapeutic strategy for this aggressive cancer subtype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) lacks ER, PR, and HER2 expression, accounting for significant mortality.
  • Estrogen receptor-beta (ERβ) and Insulin-like Growth Factor 2 (IGF2) are proposed key players in TNBC.
  • Racial disparities exist in TNBC, with higher prevalence and mortality in African American (AA) women.

Purpose of the Study:

  • To investigate the role of ERβ and IGF2 in TNBC pathogenesis.
  • To explore ERβ and IGF2 as potential therapeutic targets for TNBC.
  • To examine racial differences in ERβ and IGF2 expression in TNBC.

Main Methods:

  • Immunohistochemistry analysis of ERβ and IGF2 expression in over 250 TNBC patient tissue microarrays (TMAs).
  • Correlation of ERβ and IGF2 expression with clinical outcomes.
  • In vitro studies using TNBC cell lines (Caucasian and African American) to assess proliferation and migration under hormonal and growth factor regulation.

Main Results:

  • Higher ERβ and IGF2 expression observed in African American TNBC patient TMAs compared to Caucasian.
  • ERβ and IGF2 were significantly upregulated in TNBC cell lines.
  • ERβ agonist treatment increased proliferation and migration in TNBC cells; IGF2 upregulated ERβ transcription.

Conclusions:

  • The IGF2/ERβ axis is implicated in TNBC pathogenesis, especially in African American patients.
  • ERβ and IGF2 represent potential therapeutic targets for aggressive TNBC.
  • Further understanding of the IGF2/ERβ pathway could lead to novel treatment strategies for TNBC.
Keywords:
DPNestrogen receptor-betaestrogen receptor-beta signalinginsulin-like growth factor 2triple negative breast cancer

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