Multiple proliferation-survival signalling pathways are simultaneously active in BRAF V600E mutated thyroid carcinomas

Exp Mol Pathol. 2015 Dec;99(3):492-7. doi: 10.1016/j.yexmp.2015.09.006. Epub 2015 Sep 25.

Abstract

Background and objectives: BRAF is an oncogene which involves in pathogenesis of many thyroid carcinomas.The aim of our study was to investigate whether the downstream signalling pathway of BRAF and AKT kinase signalling pathways were active in BRAF V600E mutated thyroid carcinoma cells.

Methods: Five thyroid (papillary and undifferentiated) carcinoma cell lines and one non-cancer thyroid cell line were screened for their BRAF V600E mutation status by immunofluorescent staining and Western blot. BRAF V600E mutated thyroid carcinoma cell lines were used to test the activation status of both ERK and AKT kinase proteins through immunofluorescent studies and Western blots.

Results: Expressions of BRAF V600E mutated protein were confirmed in four thyroid (papillary and undifferentiated) carcinoma cell lines. In these cell lines, both active ERK and active AKT kinase proteins were found in BRAF V600E mutated thyroid carcinoma cells by immunofluorescent staining and Western blots experiments.

Conclusions: In BRAF V600E mutated thyroid carcinomas, active ERK and active AKT kinase proteins were noted. They are able to stimulate multiple downstream signalling pathways which ultimately result in increased proliferation and survival activities for cancer cells. Therefore, consideration needs to put on multiple targets when deciding molecular target therapies for patients with BRAF V600E mutated thyroid carcinoma.

Keywords: AKT; BRAF; ERK; Thyroid carcinoma; cell signalling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • MAP Kinase Signaling System / genetics
  • Mutation / genetics*
  • Oncogene Protein v-akt / metabolism
  • Proto-Oncogene Proteins B-raf / genetics*
  • Signal Transduction / genetics*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • BRAF protein, human
  • Oncogene Protein v-akt
  • Proto-Oncogene Proteins B-raf