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Updated: Feb 4, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

18.9K

Tumor-associated macrophages suppress estrogen receptor-β expression in triple-negative breast cancer through the

Qiulei Zhang1,2, Di Guo3, Gaoran Xu1,2

  • 1Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.

Experimental and Therapeutic Medicine
|February 2, 2026
PubMed

Insights

Tumor-associated macrophages suppress Estrogen Receptor-beta (ERβ) in triple-negative breast cancer (TNBC) via the PI3K/AKT/FOXO3a pathway. Targeting this axis may offer new therapies for aggressive TNBC.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis.
  • Estrogen Receptor-beta (ERβ) has demonstrated anti-tumor properties.
  • Reduced ERβ expression in TNBC and its regulatory mechanisms are not well understood.

Purpose of the Study:

  • To investigate the role of tumor-associated macrophages (TAMs) in ERβ downregulation in TNBC.
  • To elucidate the molecular mechanisms linking TAMs, ERβ, and TNBC progression.
  • To explore potential therapeutic strategies targeting the identified pathway.

Main Methods:

  • Bioinformatics analysis of ERβ expression in TNBC.
  • In vitro co-culture systems of TAMs and TNBC cells.
  • Orthotopic mouse models of TNBC.
  • Investigation of the PI3K/AKT/FOXO3a signaling pathway.
  • Assessment of ERβ activation and PI3K/AKT inhibition effects on TNBC metastasis.

Main Results:

  • ERβ expression is significantly lower in TNBC tissues compared to normal tissues.
  • TAMs suppress ERβ expression in TNBC cells.
  • TAMs activate the PI3K/AKT pathway, which inhibits FOXO3a binding to the ESR2 promoter, reducing ERβ expression.
  • Inhibition of PI3K/AKT signaling restores ERβ expression.
  • Combined PI3K/AKT inhibition and ERβ activation reduced TNBC cell metastasis.

Conclusions:

  • TAMs promote TNBC progression by downregulating ERβ expression via the PI3K/AKT/FOXO3a axis.
  • Targeting the PI3K/AKT pathway in combination with ERβ agonists presents a promising therapeutic strategy for TNBC.
Keywords:
ERβPI3K/AKT pathwaymouse modeltriple-negative breast cancertumor-associated macrophages

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