Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells.
Fiche publication
Date publication
octobre 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIDSON Irwin
Tous les auteurs :
Goodall J, Carreira S, Denat L, Kobi D, Davidson I, Nuciforo P, Sturm RA, Larue L, Goding CR
Lien Pubmed
Résumé
The origin of tumor heterogeneity is poorly understood, yet it represents a major barrier to effective therapy. In melanoma and in melanocyte development, the microphthalmia-associated transcription factor (Mitf) controls survival, differentiation, proliferation, and migration/metastasis. The Brn-2 (N-Oct-3, POU3F2) transcription factor also regulates melanoma proliferation and is up-regulated by BRAF and beta-catenin, two key melanoma-associated signaling molecules. Here, we show that Brn-2 also regulates invasiveness and directly represses Mitf expression. Remarkably, in melanoma biopsies, Mitf and Brn-2 each mark a distinct subpopulation of melanoma cells, providing a striking illustration of melanoma tumor heterogeneity with implications for melanoma therapy.
Référence
Cancer Res. 2008 Oct 1;68(19):7788-94.