IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Contribution of alpha2-adrenoceptors to the mitogenic effect of catecholestrogen in human breast cancer MCF-7 cells
Autor/es:
CHIESSA IJ; CASTILLO LF; LUTHY IA.
Revista:
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Editorial:
Pergamon Press
Referencias:
Lugar: Oxford; Año: 2008 vol. 110 p. 170 - 175
ISSN:
0960-0760
Resumen:
Catecholestrogens are estrogen metabolites formed by hydroxylation of 17alpha-estradiol and estrone at either the C-2 or C-4 position, rivaling the parent estrogens in concentration. The objective of the present work was to assess if their catechol group could make them induce proliferation of human breast cancer cells via alpha2-adrenoceptors. In competition studies in human breast cancer MCF-7 cells, high concentrations of 2-hydroxy-estradiol (2-OH-E2), 2-hydroxy-estrone (2-OH-E1) and 4-hydroxy-estrone (4-OH-E1) competed for [3H]-rauwolscine binding, whereas 4-hydroxy-estradiol (4-OH-E2) did not. The contribution of alpha2-adrenoceptors and estrogen receptors (ERs) in proliferation enhancement was analyzed with specific antagonists. The specific alpha2-adrenergic antagonist yohimbine partially reversed the effect of catecholestrogens except 4-OH-E2. The selective ER downregulator ICI-182780 or fulvestrant partially or totally reversed the effect of all hydroxylated catecholestrogens. When analyzing the effect of the combination of both antagonists in MCF-7, the contribution of the alpha2-adrenoceptors and ERs for 2-OH-E2, 2-OH-E1 and 4-OH-E1 was mixed, whereas for 4-OH-E2, the only receptor implied was an ER. In MDA-MB-231 cells (ER-a negative) the proliferation stimulation by these three catecholestrogens and reversal by the adrenergic antagonist was also observed. It can be concluded that alpha2-adrenoceptors contribute at least in part to the mitogenic effect of 2-OH-E2, 2-OH-E1 and 4-OH-E1.