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Oncogenic BRAF regulates oxidative metabolism via PGC1alpha and MITF

ABSTRACT: We evaluated two matched human cell lines derived from primary melanocytes, termed pmel+BRAF(V600E) and pmel+BRAF(V600E)+MITF. These cells are therefore isogenic with the exception of the expression of MITF. Gene Set Enrichment Analysis of microarray data identified a highly significant induction of oxidative phosphorylation gene set in MITF expressing cells compared to control cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Hans WIDLUND

PROVIDER: E-GEOD-38007 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF.

Haq Rizwan R Shoag Jonathan J Andreu-Perez Pedro P Yokoyama Satoru S Edelman Hannah H Rowe Glenn C GC Frederick Dennie T DT Hurley Aeron D AD Nellore Abhinav A Kung Andrew L AL Wargo Jennifer A JA Song Jun S JS Fisher David E DE Arany Zolt Z Widlund Hans R HR

Cancer cell 20130307 3

Activating mutations in BRAF are the most common genetic alterations in melanoma. Inhibition of BRAF by small molecules leads to cell-cycle arrest and apoptosis. We show here that BRAF inhibition also induces an oxidative phosphorylation gene program, mitochondrial biogenesis, and the increased expression of the mitochondrial master regulator, PGC1α. We further show that a target of BRAF, the melanocyte lineage factor MITF, directly regulates the expression of PGC1α. Melanomas with activation of ...[more]

PMID: 23477830

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