MITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma

Tine N. Alver; Timothy J. Lavelle; Ane S. Longva; Geir F. Øy; Eivind Hovig; Sigurd L. Bøe

doi:10.18632/oncotarget.10422

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Research Papers:

MITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma

Tine N. Alver _, Timothy J. Lavelle, Ane S. Longva, Geir F. Øy, Eivind Hovig and Sigurd L. Bøe

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Oncotarget. 2016; 7:55128-55140. https://doi.org/10.18632/oncotarget.10422

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Abstract

Tine N. Alver1, Timothy J. Lavelle1, Ane S. Longva1, Geir F. Øy1, Eivind Hovig1,2,3, Sigurd L. Bøe1

1Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway

2Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

3Department of Informatics, University of Oslo, Oslo, Norway

Correspondence to:

Tine N. Alver, email: [email protected]

Keywords: MITF, ERBB3, NRG1-beta, PI3K signaling, melanoma

Received: March 11, 2016 Accepted: June 27, 2016 Published: July 06, 2016

ABSTRACT

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.

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Research Papers:

MITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma

Abstract