Nelson Erik R, Chang Ching-yi, McDonnell Donald P
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, IL 61801, USA.
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Trends Endocrinol Metab. 2014 Dec;25(12):649-55. doi: 10.1016/j.tem.2014.10.001. Epub 2014 Nov 4.
Cholesterol is a risk factor for breast cancer although the mechanisms by which this occurs are not well understood. One hypothesis is that dyslipidemia results in increased cholesterol content in cell membranes, thus impacting upon membrane fluidity and subsequent signaling. In addition, studies demonstrate that the metabolite, 27-hydroxycholesterol (27HC), can function as an estrogen, increasing the proliferation of estrogen receptor (ER)-positive breast cancer cells. This was unexpected because 27HC and other oxysterols activate the liver X receptors (LXR), resulting in a reduction of intracellular cholesterol. Resolution of this paradox will require dissection of the molecular mechanisms by which ER and LXR converge in breast cancer cells. Regardless, the observation that 27HC influences breast cancer provides a rationale for strategies that target cholesterol metabolism.
胆固醇是乳腺癌的一个风险因素，尽管其发生机制尚未完全明确。一种假说认为，血脂异常会导致细胞膜中胆固醇含量增加，从而影响膜流动性及后续信号传导。此外，研究表明，代谢产物27-羟基胆固醇（27HC）可发挥雌激素的作用，增加雌激素受体（ER）阳性乳腺癌细胞的增殖。这一发现出人意料，因为27HC和其他氧化甾醇会激活肝脏X受体（LXR），导致细胞内胆固醇减少。要解决这一矛盾，需要深入研究ER和LXR在乳腺癌细胞中相互作用的分子机制。无论如何，27HC影响乳腺癌这一观察结果为针对胆固醇代谢的治疗策略提供了理论依据。
