The contribution of cholesterol and epigenetic changes to the pathophysiology of breast cancer

Publication date: Available online 4 May 2018Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Maliha T. Munir, Christopher Ponce, Catherine A. Powell, Kaiser Tarafdar, Teru Yanagita, Mahua Choudhury, Lauren S. Gollahon, Shaikh M. RahmanAbstractBreast cancer is one of the most commonly diagnosed cancers in women. Accumulating evidence suggests that cholesterol plays an important role in the development of breast cancer. Even though the mechanistic link between these two factors is not well understood, one possibility is that dysregulated cholesterol metabolism may affect lipid raft and membrane fluidity and can promote tumor development. Current studies have shown oxysterol 27-hydroxycholesterol (27-HC) as a critical regulator of cholesterol and breast cancer pathogenesis. This is supported by the significantly higher expression of CYP27A1 (cytochrome P450, family 27, subfamily A, polypeptide 1) in breast cancers. This enzyme is responsible for 27-HC synthesis from cholesterol. It has been shown that 27-HC can not only increase the proliferation of estrogen receptor (ER)-positive breast cancer cells but also stimulate tumor growth and metastasis in several breast cancer models. This phenomenon is surprising since 27-HC and other oxysterols generally reduce intracellular cholesterol levels by activating the liver X receptors (LXRs). Resolving this paradox will elucidate molecular pathways by which cholesterol, ER, and LXR are connected to breast cance...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research