The Brn-2 Transcription Factor Links Activated BRAF to Melanoma Proliferation

Jane Goodall, Claudia Wellbrock, Timothy J. Dexter, Karen Roberts, Richard Marais, Colin R. Goding

Research output: Contribution to journalArticlepeer-review

Abstract

Malignant melanoma, an aggressive and increasingly common cancer, is characterized by a strikingly high rate (70%) of mutations in BRAF, a key component of the mitogen-activated protein (MAP) kinase signaling pathway. How signaling events downstream from BRAF affect the underlying program of gene expression is poorly understood. We show that the Brn-2 POU domain transcription factor is highly expressed in melanoma cell lines but not in melanocytes or melanoblasts and that overexpression of Brn-2 in melanocytes results in increased proliferation. Expression of Brn-2 is strongly upregulated by Ras and MAP kinase signaling. Importantly, the Brn-2 promoter is stimulated by kinase-activating BRAF mutants and endogenous Brn-2 expression is inhibited by RNA interference-mediated downregulation of BRAF. Moreover, silent interfering RNA-mediated depletion of Brn-2 in melanoma cells expressing activated BRAF leads to decreased proliferation. The results suggest that the high levels of Brn-2 expression observed in melanomas link BRAF signaling to increased proliferation.
Original languageEnglish
Pages (from-to)2923-2931
Number of pages8
JournalMolecular and Cellular Biology
Volume24
Issue number7
DOIs
Publication statusPublished - Apr 2004

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