Prostaglandin E₂ down-regulates sirtuin 1 (SIRT1), leading to elevated levels of aromatase, providing insights into the obesity-breast cancer connection.

ABSTRACT: 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 E₂ (PGE₂) 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

SUBMITTER: Subbaramaiah K 

PROVIDER: S-EPMC6322870 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature