DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2005-03-01 - Article/Dans un journal avec peer-review - Anglais - 13 page(s)

Laïos Ioanna, Journé Fabrice, Nonclercq Denis , Salazar Vidal D., Toillon Robert-Alain, Laurent Guy , Leclercq Guy, "Role of the proteasome in the regulation of estrogen receptor alpha turnover and function in MCF-7 breast carcinoma cells" in Journal of Steroid Biochemistry & Molecular Biology, 94, 4, 347-359

  • Edition : Pergamon Press, Oxford (United Kingdom)
  • Codes CREF : Histologie (DI3212), Cancérologie (DI3349)
  • Unités de recherche UMONS : Histologie (M118)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
Texte intégral :

Abstract(s) :

(Anglais) Estrogen receptor a (ER) turnover in MCF-7 cells was assessed by pulse chase analysis and measurement of ER steady-state level. In untreated cells, degradation of 35S-labeled ER was characterized by a slow phase followed by a more rapid decline. Without ligand, ER elimination was totally compensated by synthesis which maintained receptor homeostasis. Estradiol (E2) and the pure antiestrogen RU 58,668 abolished the slow phase of ER breakdown and enhanced the degradation of neosynthesized ER, producing a low ER steady-state level. By contrast, the partial antiestrogen OH-Tam was ineffective in this respect and caused ER accumulation. Regardless of the conditions, ER breakdown was abolished by proteasome inhibition (MG-132). ER ligands decreased cell capacity to bind [3H]E2, even in the presence of MG-132, indicating that the regulation of ER level and E2 binding capacity occurs through distinct mechanisms. MG-132 partially blocked the basal transcription of an ERE-dependent reporter gene and modified the ability of E2 to induce the expression of the latter: the hormone was unable to restore the transactivation activity measured without MG-132. RU 58,668 and OH-Tam failed to enhance the inhibitory action of MG-132, suggesting that a loss of basal ER-mediated transactivation mainly affects the stimulatory effect of estrogens. Overall, our findings reveal that ER steady state level, ligand binding capacity and transactivation potency fit in a complex regulatory scheme involving distinct mechanisms, which may be dissociated from each other under various treatments.

Identifiants :
  • DOI : 10.1016/j.jsbmb.2005.02.005
  • PMID : 15857754