title: ERK phosphorylation is not increased in papillary thyroid carcinomas with BRAF(V600E) mutation compared to that of corresponding normal thyroid tissues.
abstract: BACKGROUND
  An association between a BRAF(V600E) mutation and upregulation of mitogen-activated protein kinase (MAPK) pathways in human papillary thyroid carcinoma (PTC) tissues has not been demonstrated well outside of in vitro studies. The aims of this study were to evaluate the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) in human PTCs with BRAF(V600E) mutations compared to that of corresponding normal thyroid tissue and to determine the expressions of Raf kinase inhibitor protein (RKIP) and MAPK phosphatase 3 (MKP-3), possible regulators of ERK1/2 activation.
  
  
  METHODS
  We analyzed the presence of BRAF(V600E) mutation and the expressions of BRAF, total ERK, p-ERK, RKIP, and MKP-3 in 33 PTCs and corresponding normal thyroid gland tissues using western blot analysis.
  
  
  RESULTS
  BRAF(V600E) mutation was found in 28 (84.8%) of 33 PTCs, 96.4% (27/28) of which showed decreased p-ERK activity, while 75% (21/28) showed increased MKP-3 expression. There were significant differences in p-ERK and MKP-3 expressions between BRAF(V600E) (+) PTCs and normal thyroid glands (p < 0.001). There were no differences in expressions of BRAF, total ERK, and RKIP between PTCs and normal thyroid tissue, irrespective of the presence of BRAF(V600E) mutation.
  
  
  CONCLUSIONS
  In human BRAF(V600E) (+) PTCs, ERK phosphorylation is decreased compared to normal thyroid glands and the observed decrease in ERK1/2 MAPK phosphorylation in BRAF(V600E) (+) PTCs may be associated with increased MKP-3 activity.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Ji In
authors.initials: JI
authors.lastname: Lee
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Jang
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Choe
authors.forename: Jung-Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Jee Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Kyu Yeon
authors.initials: KY
authors.lastname: Hur
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics; D010766:Phosphorylation / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases