title: Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.
abstract: The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.
authors.affiliation: Laboratorio de Nutrición y Regulación Metabólica, INTA-Universidad de  Chile , Santiago 7830489;
authors.forename: Pamela
authors.initials: P
authors.lastname: Cruz
authors.forename: Cristian
authors.initials: C
authors.lastname: Torres
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Ramírez
authors.forename: María José
authors.initials: MJ
authors.lastname: Epuñán
authors.forename: Luis Emilio
authors.initials: LE
authors.lastname: Valladares
authors.forename: Walter Daniel
authors.initials: WD
authors.lastname: Sierralta