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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Goodall J,Wellbrock C,Dexter TJ,Roberts K,Marais R,Goding CRdoi
10.1128/mcb.24.7.2923-2931.2004subject
Has Abstractpub_date
2004-04-01 00:00:00pages
2923-31issue
7eissn
0270-7306issn
1098-5549journal_volume
24pub_type
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