ERK Phosphorylation Is Not Increased in Papillary Thyroid Carcinomas with BRAF(V600E) Mutation Compared to That of Corresponding Normal Thyroid Tissues

作者：Kim Sun Wook; Kim Hee Kyung; Lee Ji In; Jang Hye Won; Choe Jun Ho; Kim Jung Han; Kim Jee Soo; Hur Kyu Yeon; Kim Jae Hyeon; Chung Jae Hoon^*

来源：Endocrine Research, 2013, 38(2): 89-97.

DOI：10.3109/07435800.2012.723292

• Thyroid neoplasm
• Adenocarcinoma
• Papillary
• BRAF
• Mitogen-activated protein kinase

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 %26lt; 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.

• 出版日期2013