Journal
CELL REPORTS
Volume 5, Issue 3, Pages 637-645Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2013.10.006
Keywords
-
Categories
Funding
- Department of Defense [W81XWH-09-1-0263]
- Mary Kay Foundation
- CPRIT [RP101251]
- Robert A. Welch Foundation [I-0971]
- Effie Marie Cain Research Scholarship
- Simmons Comprehensive Cancer Center Tissue Repository
- [R01HL087564]
- [U54-GM0-069338]
- [R01HL020948]
- [R01CA152301]
Ask authors/readers for more resources
To date, estrogen is the only known endogenous estrogen receptor (ER) ligand that promotes ER+ breast tumor growth. We report that the cholesterol metabolite 27-hydroxycholesterol (27HC) stimulates MCF-7 cell xenograft growth in mice. More importantly, in ER+ breast cancer patients, 27HC content in normal breast tissue is increased compared to that in cancer-free controls, and tumor 27HC content is further elevated. Increased tumor 27HC is correlated with diminished expression of CYP7B1, the 27HC metabolizing enzyme, and reduced expression of CYP7B1 in tumors is associated with poorer patient survival. Moreover, 27HC is produced by MCF-7 cells, and it stimulates cell-autonomous, ER-dependent, and GDNF-RET-dependent cell proliferation. Thus, 27HC is a locally modulated, non-aromatized ER ligand that promotes ER+ breast tumor growth.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available