Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway.
AffiliationDepartment of Hematology and Medical Oncology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany
MetadataShow full item record
AbstractData 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.
CitationExpression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway. 2015, 10 (1):77-84 Target Oncol
- EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib.
- Authors: Corcoran RB, Ebi H, Turke AB, Coffee EM, Nishino M, Cogdill AP, Brown RD, Della Pelle P, Dias-Santagata D, Hung KE, Flaherty KT, Piris A, Wargo JA, Settleman J, Mino-Kenudson M, Engelman JA
- Issue date: 2012 Mar
- Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents.
- Authors: Mao M, Tian F, Mariadason JM, Tsao CC, Lemos R Jr, Dayyani F, Gopal YN, Jiang ZQ, Wistuba II, Tang XM, Bornman WG, Bollag G, Mills GB, Powis G, Desai J, Gallick GE, Davies MA, Kopetz S
- Issue date: 2013 Feb 1
- A new water soluble MAPK activator exerts antitumor activity in melanoma cells resistant to the BRAF inhibitor vemurafenib.
- Authors: Graziani G, Artuso S, De Luca A, Muzi A, Rotili D, Scimeca M, Atzori MG, Ceci C, Mai A, Leonetti C, Levati L, Bonanno E, Tentori L, Caccuri AM
- Issue date: 2015 May 1
- Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas.
- Authors: Liu F, Cao J, Wu J, Sullivan K, Shen J, Ryu B, Xu Z, Wei W, Cui R
- Issue date: 2013 Aug
- p53 Reactivation by PRIMA-1(Met) (APR-246) sensitises (V600E/K)BRAF melanoma to vemurafenib.
- Authors: Krayem M, Journe F, Wiedig M, Morandini R, Najem A, Salès F, van Kempen LC, Sibille C, Awada A, Marine JC, Ghanem G
- Issue date: 2016 Mar