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- Title
Dual specificity phosphatase 6 as a predictor of invasiveness in papillary thyroid cancer.
- Authors
Jung Uee Lee; Songmei Huang; Min Hee Lee; Seong Eun Lee; Min Jeong Ryu; Soung Jung Kim; Yong Kyung Kim; Seul Young Kim; Kyong Hye Joung; Jin Man Kim; Minho Shong; Young Suk Jo
- Abstract
Objective: The genetic mutations causing the constitutive activation of MEK/ERK have been regarded as an initiating factor in papillary thyroid carcinoma (PTC). The ERK-specific dual specificity phosphatase 6 (DUSP6) is part of the ERK-dependent transcriptional output. Therefore, the coordinated regulation of the activities of ERK kinases and DUSP6 may need to be reestablished to make new balances in PTC. Methods: To investigate the role of DUSP6 in the regulation of ERK1/2 (MAPK3/1)-dependent transcription, 42 benign neoplasms and 167 PTCs were retrospectively analyzed by immunohistochemistry with dideoxy sequencing to detect BRAFV600E mutation. Results: The expressions of total ERK1/2, DUSP6, c-Fos (FOS), c-Myc (MYC), cyclin D1, and PCNAwere markedly increased in PTC compared with those in benign neoplasms. However, phospho-ERK1/2 was detected in only eight (4.8%) cases out of 167 PTC samples. Unexpectedly, the staining intensity and nuclear localization of ERK1/2 were not affected by the presence or absence of the BRAFV600E mutation. However, the expressions of c-Fos and PCNA were elevated in BRAFV600E-positive PTC compared with those in BRAFV600E-negative PTC. Interestingly, the higher staining intensities of DUSP6 were associated with the level of total ERK1/2 expression (PZ0.04) and with high-risk biological features such as age (PZ0.05), tumor size (PZ0.01), and extrathyroidal extension (linear by linear association, PZ0.02). In addition, DUSP6 silencing significantly decreased the cell viability and migration rate of FRO cells. Conclusions: The coordinated upregulation of total ERK1/2 and its phosphatase, DUSP6, is related to bare detection of phospho-ERK1/2 in PTC regardless of BRAFV600E mutation status. A link between DUSP6 expression and high-risk features of PTC suggested that DUSP6 is an important independent factor affecting the signaling pathways in established PTC.
- Subjects
PHOSPHATASES; THYROID cancer; GENETIC mutation; IMMUNOHISTOCHEMISTRY; GENE expression; PREVENTIVE Cardiovascular Nurses Association
- Publication
European Journal of Endocrinology, 2012, Vol 167, Issue 1, p93
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-12-0010