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

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00350760
Contributor : Maité Peney <>
Submitted on : Tuesday, February 3, 2009 - 3:33:21 PM
Last modification on : Tuesday, July 21, 2020 - 3:59:00 AM

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Jane Goodall, Suzanne Carreira, Laurence Denat, Dominique Kobi, Irwin Davidson, et al.. Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells.. Cancer Research, American Association for Cancer Research, 2008, 68 (19), pp.7788-94. ⟨10.1158/0008-5472.CAN-08-1053⟩. ⟨inserm-00350760⟩

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