27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth.

27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth.
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27-羟基胆固醇促进细胞自主,ER阳性乳腺癌的生长。

DOI:
10.1016/j.celrep.2013.10.006
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发表时间:
2013-11-14
期刊:
影响因子:
8.8
通讯作者:
Shaul PW
Shaul PW
中科院分区:
生物学1区
文献类型:
--
作者:
Wu Q;Ishikawa T;Sirianni R;Tang H;McDonald JG;Yuhanna IS;Thompson B;Girard L;Mineo C;Brekken RA;Umetani M;Euhus DM;Xie Y;Shaul PW

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到目前为止,雌激素是唯一已知的促进ER+乳腺肿瘤生长的内源性雌激素受体(ER)配体。我们报道了胆固醇代谢产物27-羟基胆固醇(27HC)对小鼠MCF-7细胞异种移植生长的刺激作用。更重要的是,在ER+乳腺癌患者中,正常乳腺组织中的27HC含量比无癌对照组增加,肿瘤组织中的27HC含量进一步升高。肿瘤27HC的增加与27HC代谢酶CYP7B1的表达减少有关,而肿瘤中的CYP7B1的表达减少与患者的生存不良有关。此外,27HC是由MCF-7细胞产生的,它刺激细胞自主的、ER依赖的和GDNF-RET依赖的细胞增殖。因此,27HC是一种局部调节的、非芳香化的ER配体,可以促进ER+乳腺肿瘤的生长。
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.
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