Abstract
Abstract B-RafV600E oncogene mutation occurs most commonly in papillary thyroid cancer (PTC), and is associated with tumor initiation. However, a genetic modification by B-RafV600E in the thyrocytes results in oncogene induced senescence (OIS). In the present study, therefore, we attempted to evaluate the factors involved in the senescence overcome program in PTC. First of all, we observed downregulation of p-Erk1/2 and upregulation of dual specific phosphatase 6 (DUSP6) in the PTC with B-RafV600E mutation. In B-RafV600E expressing thyrocytes, although DUSP6 mRNA was upregulated, its protein and phosphatase activity were similar to those of normal thyrocytes. However, DUSP6 activity was reactivated when ROS was downregulated by thyroid stimulating hormone (TSH). Moreover, upregulation of MnSOD by TSH was observed in thyrocytes and PTC. Although serum TSH was not increased, its receptor was markedly upregulated in PTC with B-RafV600E. TSH together with DUSP6 inhibited B-RafV600E induced senescence in the thyrocytes, and reactivated Ras/Akt/GSK3β resulted in c-Myc protein stabilization by inhibition of its degradation. These observations led us to conclude that increased TSH signaling by overexpression of TSH receptor is essential for B-RafV600E induced papillary thyroid carcinogenesis. Citation Format: Young Hwa Kim, Yong Won Choi, Jang-Hee Kim, Tae Jun Park. Increased TSH signaling by overexpressed thyrotrophin receptor is essential for B-RafV600E induced thyroid carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3515. doi:10.1158/1538-7445.AM2014-3515
Published Version
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