Extracellular superoxide dismutase is a thyroid differentiation marker down-regulated in cancer.
Reactive oxygen species, specifically hydrogen peroxide (H(2)O(2)), have a significant role in hormone production in thyroid tissue. Although recent studies have demonstrated that dual oxidases are responsible for the H(2)O(2) synthesis needed in thyroid hormone production, our data suggest a pivotal role for superoxide dismutase 3 (SOD3) as a major H(2)O(2)-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-Ca(2+) 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.
Laatikainen
Lilja E
LE
Cellular Therapy Group, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, Finland.
Castellone
Maria D
MD
Hebrant
Aline
A
Hoste
Candice
C
Cantisani
Maria C
MC
Laurila
Juha P
JP
Salvatore
Giuliana
G
Salerno
Paolo
P
Basolo
Fulvio
F
Näsman
Johnny
J
Dumont
Jacques E
JE
Santoro
Massimo
M
Laukkanen
Mikko O
MO
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002454:Cell Differentiation; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic; D013961:Thyroid Gland / Q000201:enzymology / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013481:Superoxides; D006861:Hydrogen Peroxide; C441642:SOD3 protein, human; C499089:Sod3 protein, rat; D013482:Superoxide Dismutase; D002118:Calcium