Science：揭示胆固醇如何影响乳腺癌风险

一项新的研究显示，因高胆固醇浓度而有着较高乳腺癌风险的妇女的命运可能会受到某种特定胆固醇代谢物——或其分解产物的支配。

研究显示，肥胖且有着高胆固醇浓度的绝经后妇女有着较高的罹患乳腺癌的风险。但科学家们对为什么会这样并不理解。如今，Erik R. Nelson等人在小鼠中显示，一种被称作27HC的特定的胆固醇代谢物会促进乳腺肿瘤的生长和转移。当罹患乳腺肿瘤的小鼠被每日注射27HC时，它们的肿瘤会比那些对照小鼠的肿瘤长的更快。

研究人员说，这种情况之所以发生是因为27HC可帮助激活2种受体——雌激素受体和肝X受体——这些受体必须受到激发才会使肿瘤生长和扩散。为了进一步地探索27HC在肿瘤生长中的作用，研究人员转而使用人类的乳腺癌样本并发现，最具浸润性的肿瘤往往会表达最高水平的能将胆固醇转化为27HC的酶。Nelson及其同事的工作提示，胆固醇会通过27HC代谢物来影响乳腺癌；该代谢物除了自然地循环之外还能直接在肿瘤相关性巨噬细胞中直接产生；在巨噬细胞中，该将胆固醇转化为27HC的酶出名地丰富。

这些结果可能对乳腺癌的治疗（有一天治疗可能会以该胆固醇转化酶为标靶）及还有预防有意义，从而提示降低胆固醇是有帮助的，尽管对降胆固醇药物与乳腺癌风险之间的关系需要继续进行研究。（转化医学网360zhyx.com）

原文链接：

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27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology
Hypercholesterolemia is a risk factor for estrogen receptor (ER)–positive breast cancers and is associated with a decreased response of tumors to endocrine therapies. Here， we show that 27-hydroxycholesterol (27HC)， a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand， increases ER-dependent growth and LXR-dependent metastasis in mouse models of breast cancer. The effects of cholesterol on tumor pathology required its conversion to 27HC by the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1 inhibitors. In human breast cancer specimens， CYP27A1 expression levels correlated with tumor grade. In high-grade tumors， both tumor cells and tumor-associated macrophages exhibited high expression levels of the enzyme. Thus， lowering circulating cholesterol levels or interfering with its conversion to 27HC may be a useful strategy to prevent and/or treat breast cancer.

来源：EurekAlert