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

First Author  Goodall J Year  2004
Journal  Mol Cell Biol Volume  24
Issue  7 Pages  2915-22
PubMed ID  15024079 Mgi Jnum  J:89066
Mgi Id  MGI:3038034 Doi  10.1128/MCB.24.7.2915-2922.2004
Citation  Goodall J, et al. (2004) Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin. Mol Cell Biol 24(7):2915-22
abstractText  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.
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