Aberrant expression of selenoproteins in the progression of colorectal cancer.
Since damage to DNA and other cellular molecules by reactive oxygen species ranks high as a major culprit in the onset and development of colorectal cancer, the aim of the present study is to clarify the role of antioxidant seleonoproteins including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and selenoprotein P (SePP), and the effect of oxidative stress on the progression of colorectal cancer. Expression of 14 oxidative stress-related molecules in both tumorous and non-tumorous tissues in 41 patients was examined by immunohistochemistry and Western blot analysis. Expression levels of proteins modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), and the positive rate of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in tumorous tissues were much higher than those in non-tumorous tissues. Glutathione (GSH) content in tumor tissues was much lower than that in non-tumorous tissues. Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly decreased in tumorous tissues, whereas that of GPx-2, which is resistant to selenium deprivation, was increased. Expression of SePP was decreased at stage III and IV, compared to that of stage II. These data suggest that contrasting expression pattern of the antioxidant selenoproteins plays an important role in the progression of colorectal cancer.
Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Japan.
Yoshiyuki
Y
Murawaki
Hiroyuki
H
Tsuchiya
Takamasa
T
Kanbe
Kenichi
K
Harada
Kazuo
K
Yashima
Kimiyasu
K
Nozaka
Osamu
O
Tanida
Michimori
M
Kohno
Tomoyuki
T
Mukoyama
Eiji
E
Nishimuki
Haruhiko
H
Kojo
Tatsuya
T
Matsura
Kazuhiko
K
Takahashi
Mitsuhiko
M
Osaki
Hisao
H
Ito
Junji
J
Yodoi
Yoshikazu
Y
Murawaki
Goshi
G
Shiota
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000447:Aldehydes / Q000032:analysis; D000975:Antioxidants / Q000032:analysis*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051149:Selenoprotein P / Q000032:analysis; D051140:Selenoproteins / Q000032:analysis*; D013482:Superoxide Dismutase / Q000032:analysis; D000072105:Superoxide Dismutase-1; D013880:Thioredoxin-Disulfide Reductase / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000447:Aldehydes; D000975:Antioxidants; D018809:Proliferating Cell Nuclear Antigen; C000606290:SOD1 protein, human; D051149:Selenoprotein P; D051140:Selenoproteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C045934:4-hydroxy-2-hexenal; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D013880:Thioredoxin-Disulfide Reductase; D003849:Deoxyguanosine; D005978:Glutathione; C027576:4-hydroxy-2-nonenal