Molecular Determinants of Estrogen Receptor Alpha Stability
Abstract
We have identified a novel endogenous ligand for the estrogen receptor, that being 27-hydroxycholesterol (27HC). 27HC mimics the effects of estrogen when assayed on multiple endpoints, including target gene regulation, inducing receptor turnover in an AIB1-dependent manner, and increasing breast cancer cell proliferation. Current studies are now focused on two main areas. First, we aim to determine whether macrophages produce 27HC in sufficient quantities to affect breast cancer cell behavior. Infiltrating macrophages are associated with reduced survival from breast cancer, and we hypothesize that one explanation for this is local production of 27HC, which acts as a mitogen. Second, we are interested in identifying proteins that bind specifically to 27HC-bound ER, and then to ascertain the biological significance of these proteins as they impact ER signaling. Previous studies had determined that levels of 27HC are positively correlated to that of cholesterol. Given the current epidemic of obesity/hypercholesterolemia, our studies on the impact of 27HC on ER are crucial for our understanding of how the physiological impact of this epidemic.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2008
- Accession Number
- ADA494436
Entities
People
- Carolyn Dusell
Organizations
- Duke University