Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells.

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

https://www.ncbi.nlm.nih.gov/pubmed/18829533

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.