期刊
PLOS ONE
卷 6, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0016631
关键词
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资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [8925/2009]
- Ministero dell'Universita e Ricerca Scientifica e Tecnologica (MIUR)
Background: The hydroxylated derivatives of cholesterol, such as the oxysterols, play important roles in lipid metabolism. In particular, 25-hydroxycholesterol (25HC) has been implicated in a variety of metabolic events including cholesterol homeostasis and atherosclerosis. 25HC is detectable in human plasma after ingestion of a meal rich in oxysterols and following a dietary cholesterol challenge. In addition, the levels of oxysterols, including 25HC, have been found to be elevated in hypercholesterolemic serum. Methodology/Principal Findings: Here, we demonstrate that the estrogen receptor (ER) alpha mediates gene expression changes and growth responses induced by 25HC in breast and ovarian cancer cells. Moreover, 25HC exhibits the ER alpha-dependent ability like 17 beta-estradiol (E2) to inhibit the up-regulation of HIF-1 alpha and connective tissue growth factor by hypoxic conditions in cardiomyocytes and rat heart preparations and to prevent the hypoxia-induced apoptosis. Conclusions/Significance: The estrogen action exerted by 25HC may be considered as an additional factor involved in the progression of breast and ovarian tumors. Moreover, the estrogen-like activity of 25HC elicited in the cardiovascular system may play a role against hypoxic environments.
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