Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin.

Journal article

Constitutive activation of the Wnt/beta-catenin signaling pathway is a notable feature of a large minority of cases of malignant melanoma, an aggressive and increasingly common cancer. The identification of target genes downstream from this pathway is therefore crucial to our understanding of the disease. The POU domain transcription factor Brn-2 has been implicated in control of proliferation and melanoma survival, and its expression is strongly upregulated in melanoma. We show here that in vivo Brn-2 is expressed in melanocytes but not in embryonic day 11.5 melanoblasts and that its expression is directly controlled by the Wnt/beta-catenin signaling pathway in melanoma cell lines and in transgenic mice. Moreover, silent interfering RNA-mediated inhibition of Brn-2 expression in melanoma cells overexpressing beta-catenin results in significantly decreased proliferation. These results, together with the observation that BRAF signaling also induces Brn-2 expression, reveal that Brn-2 is a focus for the convergence of two key melanoma-associated signaling pathways that are linked to cell proliferation.

Authors: Goodall, J; Martinozzi, S; Dexter, T; Champeval, D; Carreira, S

• Publication status: Published
• Journal: Molecular and cellular biology
• Volume: 24
• Issue: 7
• Pages: 2915-2922
• Publication date: 2004-04-01
• DOI: 10.1128/mcb.24.7.2915-2922.2004
• EISSN: 1098-5549
• ISSN: 0270-7306
• Language: English
• Keywords: Proto-Oncogene Proteins c-raf; In Situ Hybridization; Melanocytes; Cytoskeletal Proteins; Recombinant Fusion Proteins; Proto-Oncogene Proteins; Embryo, Mammalian; Proto-Oncogene Proteins B-raf; Signal Transduction; beta Catenin; Homeodomain Proteins; Trans-Activators; Transcription Factors; POU Domain Factors; RNA, Small Interfering; Zebrafish Proteins; Mice; Animals; Melanoma; Mice, Transgenic; Cell Line, Tumor; Humans; Promoter Regions, Genetic; Wnt Proteins