[PDF][PDF] 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth

Q Wu, T Ishikawa, R Sirianni, H Tang, JG McDonald… - Cell reports, 2013 - cell.com
Q Wu, T Ishikawa, R Sirianni, H Tang, JG McDonald, IS Yuhanna, B Thompson, L Girard…
Cell reports, 2013cell.com
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 …
Summary
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, nonaromatized ER ligand that promotes ER+ breast tumor growth.
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