Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway.
Affiliation
Department of Hematology and Medical Oncology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, GermanyIssue Date
2015-03
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Show full item recordAbstract
Data regarding the expression of epidermal growth factor receptor (EGFR) in melanoma and its role in the tumor biology are conflicting. In BRAF V600-mutant melanomas, the expression of EGFR has been associated with acquired resistance to BRAF inhibitors. In this study, we assessed EGFR expression and downstream signaling activity in a panel of melanoma cell lines and we investigated the effects of the BRAF inhibitor vemurafenib on expression of EGFR and its downstream effectors in a subgroup of BRAF-mutant melanoma cells. Three out of 10 melanoma cell lines expressed EGFR. Downstream signaling via ERK and AKT was responsive to either stimulation by EGF or inhibition by erlotinib. Constitutive activation of ERK occurred in all the cell lines investigated whereas constitutive activation of AKT only in three cell lines. Constitutive activation of ERK and AKT was independent from EGFR expression. Vemurafenib did not affect EGFR expression in general, but it increased EGFR phosphorylation in the cell line SkMel5. Induced EGFR phosphorylation was sensitive to treatment with erlotinib. Vemurafenib efficiently blocked ERK activation in all the BRAF-mutant cell lines tested, whereas its effects on AKT activation were dissimilar in the different cell lines. Our data suggest that EGFR is functional but usually inactive in EGFR high-expressing cell lines. Basal EGFR expression unlikely represents a biomarker for predicting the sensitivity to vemurafenib in melanoma, but EGFR activation might represent a mechanism of vemurafenib resistance in a subset of melanoma cells.Citation
Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway. 2015, 10 (1):77-84 Target OncolJournal
Targeted OncologyDOI
10.1007/s11523-014-0318-9PubMed ID
24824730Type
ArticleLanguage
enISSN
1776-260Xae974a485f413a2113503eed53cd6c53
10.1007/s11523-014-0318-9