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Proc Natl Acad Sci U S A. 2016 May 31;113(22):6254-8. doi: 10.1073/pnas.1606027113. Epub 2016 May 16.

BPTF transduces MITF-driven prosurvival signals in melanoma cells.

Author information

1
Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, CA 94107;
2
Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, CA 94121;
3
Department of Dermatology and Pharmaceutical Chemistry, University of California, San Francisco, CA 94143 JCleaver@cc.ucsf.edu kashani@cpmcri.org.
4
Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, CA 94107; JCleaver@cc.ucsf.edu kashani@cpmcri.org.

Abstract

Microphthalmia-associated transcription factor (MITF) plays a critical and complex role in melanocyte transformation. Although several downstream targets of MITF action have been identified, the precise mechanisms by which MITF promotes melanocytic tumor progression are incompletely understood. Recent studies identified an oncogenic role for the bromodomain plant homeodomain finger transcription factor (BPTF) gene in melanoma progression, in part through activation of BCL2, a canonical target of MITF signaling. Analysis of the BPTF promoter identified a putative MITF-binding site, suggesting that MITF may regulate BPTF expression. Overexpression of MITF resulted in up-regulation of BPTF in a panel of melanoma and melanocyte cell lines. shRNA-mediated down-regulation of MITF in melanoma cells was accompanied by down-regulation of BPTF and BPTF-regulated genes (including BCL2) and resulted in reduced proliferative capacity of melanoma cells. The suppression of cell growth mediated by MITF silencing was rescued by overexpression of BPTF cDNA. Binding of MITF to the BPTF promoter was demonstrated using ChIP analysis. MITF overexpression resulted in direct transcriptional activation of BPTF, as evidenced by increased luciferase activity driven by the BPTF promoter. These results indicate that BPTF transduces key prosurvival signals driven by MITF, further supporting its important role in promoting melanoma cell survival and progression.

KEYWORDS:

melanoma; oncogenes; signaling cascade

PMID:
27185926
PMCID:
PMC4896689
DOI:
10.1073/pnas.1606027113
[Indexed for MEDLINE]
Free PMC Article

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