Selenoprotein expression in Hürthle cell carcinomas and in the human Hürthle cell carcinoma line XTC.UC1.
Hürthle cell carcinomas (HTC) are characterized by mitochondrial amplification and enhanced oxygen metabolism. To clarify if defects in enzymes scavenging reactive oxygen species are involved in the pathogenesis of HTC, we analyzed selenium (Se)-dependent expression of various detoxifying selenoproteins in the HTC cell line XTC.UC1. Glutathione peroxidase and thioredoxin reductase activity was found both in cell lysates and conditioned media of XTC.UC1 cells and was increased by Na(2)SeO(3). Western blot analysis demonstrated the presence of thioredoxin reductase both in cell lysates and conditioned media and of glutathione peroxidase 3 in conditioned media. Type I 5'-deiodinase, another selenoprotein that catalyzes thyroid hormone metabolism, was detectable only in cell lysates by enzyme assay and Western blot, and responded to stimulation by both Na(2)SeO(3) and retinoic acid. A selenoprotein P signal was detected in conditioned media by Western blot, but was not enhanced by Na(2)SeO(3) treatment. In situ hybridization revealed glutathione peroxidase mRNAs in HTC specimen; glutathione peroxidase 3 mRNA levels were reduced. These data suggest adequate expression and Se-dependent regulation of a couple of selenoproteins involved in antioxidant defense and thyroid hormone metabolism in XTC.UC1 cells, so far giving no evidence of a role of these proteins in the pathogenesis of HTCs.
Menth
Marianne
M
Abteilung für Molekulare Innere Medizin und Klinische Forschergruppe der Medizinischen Poliklinik, Universität Würzburg, Würzburg, Germany.
Schmutzler
Cornelia
C
Mentrup
Birgit
B
Hoang-Vu
Cuong
C
Takahashi
Kazuhiko
K
Honjoh
Tsutomu
T
Köhrle
Josef
J
D018249:Adenoma, Oxyphilic / Q000201:enzymology / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D016166:Free Radical Scavengers / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007453:Iodide Peroxidase / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051149:Selenoprotein P; D051140:Selenoproteins; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000378:metabolism*
D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D016166:Free Radical Scavengers; D010545:Peroxides; D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D007453:Iodide Peroxidase; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase