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

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2008-03-01 - Article/Dans un journal avec peer-review - Anglais - 12 page(s)

Gallo Dominique, Haddad Iman, Duvillier Hugues, Jacquemotte Françoise, Laïos Ioanna, Laurent Guy , Jacquot Yves, Vinh Joëlle, Leclercq Guy, "Trophic effect in MCF-7 cells of ERa17p, a peptide corresponding to a platform regulatory motif of the estrogen receptor a – Underlying mechanisms" in Journal of Steroid Biochemistry & Molecular Biology, 109, 1, 138-149

  • Edition : Pergamon Press, Oxford (United Kingdom)
  • Codes CREF : Histologie (DI3212), Cancérologie (DI3349)
  • Unités de recherche UMONS : Histologie (M118)
Texte intégral :

Abstract(s) :

(Anglais) As yet, estrogen receptor alpha (ERalpha) inhibitors used in clinical practice target a unique site, i.e. the hormone-binding pocket. With the aim of discovering other potential therapeutic targets in the receptor, we studied its AF-2a domain, a site that proves to be critical for ligand-independent ERalpha activity. Previous studies from our laboratory highlighted an auto-inhibitory action associated with a site included in this domain, i.e. the P295-T311 sequence. Accordingly, a deletion of this sequence produces a constitutively activated receptor mutant. More interestingly, a synthetic peptide with the P295-T311 sequence (ERalpha17p) elicits in breast cancer cell lines estrogenic responses that may be ascribed to a competitive mechanism towards the P295-T311-associated auto-inhibition of ERalpha. In the present study, we show that ERalpha17p sustains MCF-7 cell growth in estrogen-depleted culture medium by inducing molecular events promoting G1/S phase transition. We demonstrate, moreover, that this proliferative activity is associated with receptor down regulation (acceleration of ERalpha degradation and repression of ESR1 gene transcription), similar to that induced by estrogen agonists. Complementary studies suggest that our observations may be, at least in part, relevant to a competitive inhibition affecting ERalpha-Hsp70 association. Hence, the design of drugs able to stabilize ERalpha-Hsp70 complexes - where the receptor is in an inactive conformation - may be of therapeutic value.

Identifiants :
  • DOI : 10.1016/j.jsbmb.2007.12.012
  • PMID : 18262408