PPARγ antagonists induce aromatase transcription in adipose tissue cultures
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View abstract on PubMed
Summary
This summary is machine-generated.Environmental chemicals acting as PPARγ antagonists can promote breast cancer by increasing aromatase expression in adipose tissue, affecting both adipogenesis and directly upregulating aromatase.
Area Of Science
- Endocrinology
- Molecular Biology
- Environmental Health
Background
- Aromatase is crucial for estrogen biosynthesis and a risk factor for hormone receptor-positive breast cancer.
- Estrogen synthesized in adipose tissue fuels breast cancer growth in postmenopausal women.
- Peroxisome proliferator-activated receptor gamma (PPARγ) activation in adipose stromal cells (ASCs) reduces aromatase and promotes adipocyte differentiation.
Purpose Of The Study
- To investigate if PPARγ antagonists promote breast cancer by stimulating aromatase expression in human adipose tissue.
- To elucidate the mechanisms by which PPARγ antagonists affect adipogenesis and aromatase expression.
- To assess the impact of environmental PPARγ antagonists on estrogen biosynthesis.
Main Methods
- Utilized primary human adipose tissue cells and explants, alongside cell lines (A41hWAT, C3H10T1/2, H295R).
- Assessed effects on adipogenesis, aromatase expression, and estrogen biosynthesis.
- Employed Nuclear Magnetic Resonance (NMR) spectroscopy to confirm molecular interactions.
Main Results
- PPARγ antagonists inhibited adipocyte differentiation, preventing aromatase downregulation.
- DEHPA, a potent antagonist, directly interacted with PPARγ, blocking agonist binding.
- ASCs exposed to antagonists showed upregulated aromatase, particularly in differentiated cells and human adipose tissue explants.
- Overexpression of PPARG reduced aromatase expression.
Conclusions
- Environmental PPARγ antagonists can promote breast cancer via adipose tissue aromatase upregulation.
- Two mechanisms are involved: indirect inhibition of adipogenesis and acute direct upregulation of aromatase.
- Findings highlight the role of environmental chemicals in endocrine disruption and breast cancer progression.
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