Extracellular superoxide dismutase is a thyroid differentiation marker down-regulated in cancer

被引:35
|
作者
Laatikainen, Lilja E. [1 ]
Castellone, Maria D. [2 ]
Hebrant, Aline [3 ]
Hoste, Candice [3 ]
Cantisani, Maria C. [2 ]
Laurila, Juha P. [1 ]
Salvatore, Giuliana [4 ]
Salerno, Paolo [2 ]
Basolo, Fulvio [5 ]
Nasman, Johnny [6 ]
Dumont, Jacques E. [3 ]
Santoro, Massimo [2 ]
Laukkanen, Mikko O. [1 ,7 ]
机构
[1] Univ Turku, Med Res Lab, Cellular Therapy Grp, FIN-20520 Turku, Finland
[2] Univ Naples Federico II, Inst Expt Endocrinol & Oncol CNR, Dept Biol & Cellular & Mol Pathol, I-80014 Naples, Italy
[3] Univ Libre Bruxelles, Inst Rech Interdisciplinaire Biol Humaine & Mol, B-1083 Brussels, Belgium
[4] Univ Parthenope, Dipartimento Studi Ist & Sistemi Terr, I-80133 Naples, Italy
[5] Univ Pisa, Dipartimento Chirurg, I-56126 Pisa, Italy
[6] Abo Akad Univ, FIN-20520 Turku, Finland
[7] Fdn IRCCS SDN, I-80143 Naples, Italy
基金
芬兰科学院;
关键词
TYROSINE KINASE-ACTIVITY; GROWTH-FACTOR RECEPTOR; HYDROGEN-PEROXIDE; GENE-EXPRESSION; THYROTROPIN RECEPTOR; PROTEIN-KINASE; CELL-LINE; CONGENITAL HYPOTHYROIDISM; H2O2-GENERATING SYSTEM; AUTONOMOUS ADENOMAS;
D O I
10.1677/ERC-10-0021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Reactive oxygen species, specifically hydrogen peroxide (H2O2), have a significant role in hormone production in thyroid tissue. Although recent studies have demonstrated that dual oxidases are responsible for the H2O2 synthesis needed in thyroid hormone production, our data suggest a pivotal role for superoxide dismutase 3 (SOD3) as a major H2O2-producing enzyme. According to our results, Sod3 is highly expressed in normal thyroid, and becomes even more abundant in rat goiter models. We showed TSH-stimulated expression of Sod3 via phospholipase C-Ca2+ and cAMP-protein kinase A, a pathway that might be disrupted in thyroid cancer. In line with this finding, we demonstrated an oncogene-dependent decrease in Sod3 mRNA expression synthesis in thyroid cancer cell models that corresponded to a similar decrease in clinical patient samples, suggesting that SOD3 could be used as a differentiation marker in thyroid cancer. Finally, the functional analysis in thyroid models indicated a moderate role for SOD3 in regulating normal thyroid cell proliferation being in line with our previous observations. Endocrine-Related Cancer (2010) 17 785-796
引用
收藏
页码:785 / 796
页数:12
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