Pathology & Oncology Research

, Volume 21, Issue 4, pp 957–968 | Cite as

Sensitivity of Melanoma Cells to EGFR and FGFR Activation but Not Inhibition is Influenced by Oncogenic BRAF and NRAS Mutations

  • Tamás Garay
  • Eszter Molnár
  • Éva Juhász
  • Viktória László
  • Tamás Barbai
  • Judit Dobos
  • Karin Schelch
  • Christine Pirker
  • Michael Grusch
  • Walter Berger
  • József Tímár
  • Balázs HegedűsEmail author


BRAF and NRAS are the two most frequent oncogenic driver mutations in melanoma and are pivotal components of both the EGF and FGF signaling network. Accordingly, we investigated the effect of BRAF and NRAS oncogenic mutation on the response to the stimulation and inhibition of epidermal and fibroblast growth factor receptors in melanoma cells. In the three BRAF mutant, two NRAS mutant and two double wild-type cell lines growth factor receptor expression had been verified by qRT-PCR. Cell proliferation and migration were determined by the analysis of 3-days-long time-lapse videomicroscopic recordings. Of note, a more profound response was found in motility as compared to proliferation and double wild-type cells displayed a higher sensitivity to EGF and FGF2 treatment when compared to mutant cells. Both baseline and induced activation of the growth factor signaling was assessed by immunoblot analysis of the phosphorylation of the downstream effectors Erk1/2. Low baseline and higher inducibility of the signaling pathway was characteristic in double wild-type cells. In contrast, oncogenic BRAF or NRAS mutation did not influence the response to EGF or FGF receptor inhibitors in vitro. Our findings demonstrate that the oncogenic mutations in melanoma have a profound impact on the motogenic effect of the activation of growth factor receptor signaling. Since emerging molecularly targeted therapies aim at the growth factor receptor signaling, the appropriate mutational analysis of individual melanoma cases is essential in both preclinical studies and in the clinical trials and practice.


Melanoma BRAF NRAS Mutation EGF FGF2 EGFR inhibitor FGFR inhibitor 



This work was financially supported by TAMOP 4.2.1/B-09/1/MKR-2010-0001, OTKA CNK 77649 and MOB 80325 research grants as well as by the EGT/Norwegian Financial Mechanism HU0125. BH was a Magyary Zoltán postdoctoral fellow. GT acknowledges the Ernst Mach fellowship from the Österreichischer Austauschdienst.

Supplementary material

12253_2015_9916_MOESM1_ESM.doc (116 kb)
Supplementary Figure 1 (DOC 116 kb)
12253_2015_9916_MOESM2_ESM.doc (105 kb)
Supplementary Figure 2 (DOC 105 kb)


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© Arányi Lajos Foundation 2015

Authors and Affiliations

  • Tamás Garay
    • 1
  • Eszter Molnár
    • 1
  • Éva Juhász
    • 1
  • Viktória László
    • 2
  • Tamás Barbai
    • 1
  • Judit Dobos
    • 3
    • 4
  • Karin Schelch
    • 5
  • Christine Pirker
    • 5
  • Michael Grusch
    • 5
  • Walter Berger
    • 5
  • József Tímár
    • 1
    • 6
  • Balázs Hegedűs
    • 1
    • 2
    • 6
    Email author
  1. 1.2nd Department of PathologySemmelweis UniversityBudapestHungary
  2. 2.Department of Thoracic SurgeryMedical University of ViennaViennaAustria
  3. 3.Department of Experimental PharmacologyNational Institute of OncologyBudapestHungary
  4. 4.Vichem Chemie Research LtdBudapestHungary
  5. 5.Institute of Cancer Research and Comprehensive Cancer CenterMedical University of ViennaViennaAustria
  6. 6.MTA-SE Tumor Progression Research GroupBudapestHungary

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