Related Experiment Video

Updated: Dec 26, 2025

Visualization of Estrogen Receptors in Colons of Mice with TNBS-Induced Crohn's Disease using Immunofluorescence
08:02

Visualization of Estrogen Receptors in Colons of Mice with TNBS-Induced Crohn's Disease using Immunofluorescence

Published on: March 12, 2020

7.0K

Inflammatory macrophage derived TNFα downregulates estrogen receptor α via FOXO3a inactivation in human breast cancer

Frida Björk Gunnarsdóttir1, Catharina Hagerling2, Caroline Bergenfelz1

  • 1Cancer Immunology, Department of Translational Medicine, 214 28, Malmö, Lund University, Sweden.

Experimental Cell Research
|March 8, 2020
PubMed

Insights

Tumor-associated macrophages secrete tumor necrosis factor alpha (TNFα), which reduces estrogen receptor alpha (ERα) in breast cancer cells, potentially causing endocrine resistance. TNFα inhibitors may help treat ERα-positive breast cancer.

Area of Science:

  • Oncology
  • Immunology
  • Endocrinology

Background:

  • Estrogen receptor alpha-positive (ERα+) breast cancer often develops resistance to endocrine therapy.
  • This resistance is linked to decreased ERα expression in residual cancer cells.

Purpose of the Study:

  • To investigate the mechanism by which macrophages influence ERα expression and endocrine resistance in breast cancer.
  • To explore the role of tumor necrosis factor alpha (TNFα) in ERα downregulation.

Main Methods:

  • Utilized long-term NSG xenograft models of human breast cancer.
  • Employed in vitro primary cell cultures of human monocytes and breast cancer cells.
  • Analyzed primary tumors from breast cancer patients.

Main Results:

  • Macrophage-derived TNFα was found to downregulate ERα in breast cancer cells by inactivating the transcription factor FOXO3a.
  • Tumor-associated macrophages in patient tumors correlated with ERα negativity.
  • Presence of tumor-associated macrophages indicated a worse prognosis in ERα+ breast cancer patients.

Conclusions:

  • Pro-inflammatory macrophages can promote breast cancer progression and endocrine resistance.
  • Targeting TNFα with antagonists may be a viable strategy for treating ERα+ breast cancer.
  • Further evaluation of TNFα antagonists in clinical settings is warranted.
Keywords:
Breast cancerEndocrine resistanceEstrogen receptorFOXO3aMacrophageTNFalpha

More Related Videos

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

20.6K
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

10.8K

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.3K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.5K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
2.0K