Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Genes and Development Année : 2010

Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance.

Mathieu Lupien
  • Fonction : Auteur
Clifford A Meyer
  • Fonction : Auteur
Shannon T Bailey
  • Fonction : Auteur
Jennifer Cook
  • Fonction : Auteur
Thomas Westerling
  • Fonction : Auteur
Xiaoyang Zhang
  • Fonction : Auteur
Jason S Carroll
  • Fonction : Auteur
Daniel R Rhodes
  • Fonction : Auteur
X Shirley Liu
  • Fonction : Auteur
Myles Brown
  • Fonction : Auteur

Résumé

Estrogen receptor α (ERα) expression in breast cancer is predictive of response to endocrine therapy; however, resistance is common in ERα-positive tumors that overexpress the growth factor receptor ERBB2. Even in the absence of estrogen, ERα can be activated by growth factors, including the epidermal growth factor (EGF). EGF induces a transcriptional program distinct from estrogen; however, the mechanism of the stimulus-specific response is unknown. Here we show that the EGF-induced ERα genomic targets, its cistromes, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ERα cistrome specifically regulates genes found overexpressed in ERBB2-positive human breast cancers. This provides a potential molecular explanation for the endocrine therapy resistance seen in ERα-positive breast cancers that overexpress ERBB2. These results suggest a central role for ERα in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ERα, as opposed to blocking its estrogen responsiveness alone.

Dates et versions

hal-00592324 , version 1 (12-05-2011)

Identifiants

Citer

Mathieu Lupien, Clifford A Meyer, Shannon T Bailey, Jérôme Eeckhoute, Jennifer Cook, et al.. Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance.. Genes and Development, 2010, 24 (19), pp.2219-27. ⟨10.1101/gad.1944810⟩. ⟨hal-00592324⟩
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