title: The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes.
abstract: BACKGROUND
  The hydroxylated derivatives of cholesterol, such as the oxysterols, play important roles in lipid metabolism. In particular, 25-hydroxycholesterol (25 HC) has been implicated in a variety of metabolic events including cholesterol homeostasis and atherosclerosis. 25 HC 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 25 HC, have been found to be elevated in hypercholesterolemic serum.
  
  
  RESULTS
  Here, we demonstrate that the estrogen receptor (ER) α mediates gene expression changes and growth responses induced by 25 HC in breast and ovarian cancer cells. Moreover, 25 HC exhibits the ERα-dependent ability like 17 β-estradiol (E2) to inhibit the up-regulation of HIF-1α and connective tissue growth factor by hypoxic conditions in cardiomyocytes and rat heart preparations and to prevent the hypoxia-induced apoptosis.
  
  
  CONCLUSIONS
  The estrogen action exerted by 25 HC may be considered as an additional factor involved in the progression of breast and ovarian tumors. Moreover, the estrogen-like activity of 25 HC elicited in the cardiovascular system may play a role against hypoxic environments.
authors.affiliation: Department of Pharmaco-Biology, University of Calabria, Rende, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Lappano
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Ernestina Marianna
authors.initials: EM
authors.lastname: De Francesco
authors.forename: Tommaso
authors.initials: T
authors.lastname: Angelone
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Cerra
authors.forename: Didier
authors.initials: D
authors.lastname: Picard
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism* / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D050356:Lipid Metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction
chemical_list: D047628:Estrogen Receptor alpha; D006888:Hydroxycholesterols; C007997:25-hydroxycholesterol; D002784:Cholesterol