Prostaglandin E 2 down-regulates sirtuin 1 (SIRT1), leading to elevated levels of aromatase, providing insights into the obesity-breast cancer connection.
Subbaramaiah K., Iyengar NM., Morrow M., Elemento O., Zhou XK., Dannenberg AJ.
Laboratory Study, published in J Biol Chem (2018) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Laboratory Study
- Journal
- J Biol Chem (2018)
- Country
- United States
- Reported sample size
- —
- Source database
- PubMed
- PMID
- 30409902
- DOI
- 10.1074/jbc.RA118.005866
Abstract (original English)
Obesity increases the risk of hormone receptor-positive breast cancer in postmenopausal women. Levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis, are increased in the breast tissue of obese women. Both prostaglandin E 2 (PGE 2 ) and hypoxia-inducible factor 1α (HIF-1α) contribute to the induction of aromatase in adipose stromal cells (ASCs). Sirtuin 1 (SIRT1) binds, deacetylates, and thereby inactivates HIF-1α. Here, we sought to determine whether SIRT1 also plays a role in regulating aromatase expression. We demonstrate that reduced SIRT1 levels are associated with elevated levels of acetyl-HIF-1α, HIF-1α, and aromatase in breast tissue of obese compared with lean women. To determine whether these changes were functionally linked, ASCs were utilized. In ASCs, treatment with PGE 2 , which is increased in obese individuals, down-regulated SIRT1 levels, leading to elevated acetyl-HIF-1α and HIF-1α levels and enhanced aromatase gene transcription. Chemical SIRT1 activators (SIRT1720 and resveratrol) suppressed the PGE 2 -mediated induction of acetyl-HIF-1α, HIF-1α, and aromatase. Silencing of p300/CBP-associated factor (PCAF), which acetylates HIF-1α, blocked PGE 2 -mediated increases in acetyl-HIF-1α, HIF-1α, and aromatase. SIRT1 overexpression or PCAF silencing inhibited the interaction between HIF-1α and p300, a coactivator of aromatase expression, and supp
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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