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Effect of nuclear export inhibition on estrogen receptor regulation in breast cancer cells

par Nonclercq, Denis;Journé, Fabrice ;Laïos, Ioanna;Chaboteaux, Carole ;Toillon, Robert-Alain ;Leclercq, Guy ;Laurent, Guy
Référence Journal of molecular endocrinology, 39, 1-2, page (105-118)
Publication Publié, 2007-07

Article révisé par les pairs

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Résumé :

We used the Crm1 inhibitor leptomycin B (LMB) to examine a possible involvement of nuclear export in estrogen receptor alpha (ER) level and function in MCF-7 breast carcinoma cells. As revealed by immunofluorescence microscopy and western blotting with anti-ER antibodies, LMB produced an accumulation of ER in cell nuclei. LMB also partly abrogated ER elimination resulting from Hsp90 disruption and 17beta-estradiol (E(2))-induced ER downregulation. By contrast, it was ineffective on ER downregulation caused by the pure anti-estrogen fulvestrant. Finally, LMB inhibited E(2)-induced progesterone receptor expression and the expression of an estrogen response element-driven luciferase reporter gene in unstimulated and E(2)-stimulated cells. Altogether, the data reported here suggest that: i) ER undergoes nuclear export directly or indirectly involving exportin Crm1; ii) degradation of unliganded and of agonist-bound ER probably occurs in an extranuclear compartment, while it is not the case for ER bound to a pure anti-estrogen; and iii) optimal ER-mediated gene transactivation seems to require nucleocytoplasmic shuttle of the receptor.