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.