NKX2.5 is expressed in papillary thyroid carcinomas and regulates differentiation in thyroid cells

被引:8
作者
Cardoso Penha, Ricardo Cortez [1 ,2 ]
Buexm, Luisa Aguirre [2 ]
Rodrigues, Fabiana Resende [3 ]
de Castro, Taciana Padilha [4 ]
Santos, Maria Carolina S. [1 ]
Fortunato, Rodrigo Soares [5 ]
Carvalho, Denise P. [1 ]
Cardoso-Weide, Luciene C. [3 ]
Ferreira, Andrea C. F. [1 ,6 ]
机构
[1] Univ Fed Rio de Janeiro, IBCCF, Lab Fisiol Endocrina Doris Rosenthal, Rio De Janeiro, Brazil
[2] Inst Nacl Canc Jose Alencar Gomes da Silva INCA, Ctr Pesquisas CPQ, Programa Carcinogenese Mol, Rio De Janeiro, Brazil
[3] Univ Fed Fluminense, Fac Med, Dept Patol, Rio De Janeiro, Brazil
[4] Fiocruz MS, ENSP, CESTEH, Rio De Janeiro, RJ, Brazil
[5] Univ Fed Rio de Janeiro, IBCCF, Lab Radiobiol Mol, Rio De Janeiro, Brazil
[6] Univ Fed Rio de Janeiro, NUMPEX, Campus Duque de Caxias, Rio De Janeiro, Brazil
关键词
NKX2.5; Thyroid cancer; Persistence/recurrence; Papillary thyroid carcinoma; Differentiation; Iodide uptake; H2O2; SODIUM/IODIDE SYMPORTER NIS; CANCER; OXIDASE; GENES;
D O I
10.1186/s12885-018-4399-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: NKX2.5 is a transcription factor transiently expressed during thyroid organogenesis. Recently, several works have pointed out the oncogenic role of NKX2.5 in a variety of tumors. We therefore hypothesized that NKX2. 5 could also play a role in thyroid cancer. Methods: The validation of NKX2.5 expression was assessed by immunohistochemistry analysis in a Brazilian case series of 10 papillary thyroid carcinoma (PTC) patients. Then, the long-term prognostic value of NKX2.5 and its correlation with clinicopathologic features of 51 PTC patients was evaluated in a cohort with 10-years follow-up (1990-1999). Besides, the effect of NKX2.5 overexpression on thyroid differentiation markers and function was also investigated in a non-tumor thyroid cell line (PCCL3). Results: NKX2.5 was shown to be expressed in most PTC samples (8/10, case series; 27/51, cohort). Patients who had tumors expressing NKX2.5 showed lower rates of persistence/recurrence (p = 0.013). Overexpression of NKX2.5 in PCCL3 cells led to: 1) downregulation of thyroid differentiation markers (thyrotropin receptor, thyroperoxidase and sodium-iodide symporter); 2) reduced iodide uptake; 3) increased extracellular H2O2 generation, dual oxidase 1 mRNA levels and activity of DuOx1 promoter. Conclusions: In summary, NKX2.5 is expressed in most PTC samples analyzed and its presence correlates to better prognosis of PTC. In vitro, NKX2.5 overexpression reduces the expression of thyroid differentiation markers and increases ROS production. Thus, our data suggests that NKX2.5 could play a role in thyroid carcinogenesis.
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页数:12
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