TY - JOUR
T1 - 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth
AU - Wu, Qian
AU - Ishikawa, Tomonori
AU - Sirianni, Rosa
AU - Tang, Hao
AU - McDonald, Jeffrey G.
AU - Yuhanna, Ivan S.
AU - Thompson, Bonne
AU - Girard, Luc
AU - Mineo, Chieko
AU - Brekken, Rolf A.
AU - Umetani, Michihisa
AU - Euhus, David M.
AU - Xie, Yang
AU - Shaul, Philip W.
N1 - Funding Information:
This work was supported by Department of Defense Idea Award W81XWH-09-1-0263, a grant from the Mary Kay Foundation, and R01HL087564 (P.W.S.), CPRIT RP101251 (H.T., L.G., and Y.X.), U54-GM0-069338, R01HL020948 and Robert A. Welch Foundation Grant I-0971 (J.G.M. and B.T.), R01CA152301 (H.T. and Y.X.), an Effie Marie Cain Research Scholarship (R.A.B.), and the Simmons Comprehensive Cancer Center Tissue Repository (D.M.E.).
PY - 2013
Y1 - 2013
N2 - 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
AB - 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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U2 - 10.1016/j.celrep.2013.10.006
DO - 10.1016/j.celrep.2013.10.006
M3 - Article
C2 - 24210818
AN - SCOPUS:84887617570
SN - 2211-1247
VL - 5
SP - 637
EP - 645
JO - Cell Reports
JF - Cell Reports
IS - 3
ER -