Open AccessMITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma
Author(s) -
Tine Norman Alver,
Timothy J. Lavelle,
Ane Sager Longva,
Geir Frode Øy,
Eivind Hovig,
Sigurd Leinæs Bøe
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.10422
Subject(s) - microphthalmia associated transcription factor , neuregulin 1 , erbb3 , cancer research , pi3k/akt/mtor pathway , small interfering rna , gene silencing , receptor tyrosine kinase , sox10 , biology , transcription factor , microbiology and biotechnology , chemistry , kinase , signal transduction , rna , biochemistry , gene
The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway is frequently hyper-activated upon vemurafenib treatment of melanoma. We have here investigated the relationship between SRY-box 10 (SOX10), forkhead box 3 (FOXD3) and microphthalmia-associated transcription factor (MITF) in the regulation of the receptor tyrosine-protein kinase ERBB3, and its cognate ligand neuregulin 1-beta (NRG1-beta). We found that both NRG1-beta and ERBB3 mRNA levels were elevated as a consequence of MITF depletion, induced by either vemurafenib or MITF small interfering RNA (siRNA) treatment. Elevation of ERBB3 receptor expression after MITF depletion caused increased activation of the PI3K pathway in the presence of NRG1-beta ligand. Together, our results suggest that MITF may play a role in the development of acquired drug resistance through hyper-activation of the PI3K pathway.