Overexpression of human mutT homologue gene messenger RNA in renal-cell carcinoma: evidence of persistent oxidative stress in cancer.
Data regarding oxidatively modified DNA bases suggest that cancer cells are more exposed to oxidative stress than adjacent non-tumorous tissue. This novel concept may contribute to the understanding of certain aspects of tumor biology such as activated transcription factors, genetic instability, chemotherapy-resistance and metastasis. We therefore tested this concept in human renal-cell carcinomas (RCCs) by evaluating the expression of hMTH1, an enzyme preventing the misincorporation into DNA of 8-oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate), an oxidized form of dGTP in the nucleotide pool. The expression of hMTH1 messenger RNA (mRNA) in RCC was significantly higher than that in adjacent non-tumorous kidney. Moreover, advanced-stage tumors showed significantly higher hMTH1 mRNA expression than early-stage tumors, and there was a modest linear correlation between hMTH1 expression and c-myc expression. The results provide logical support for the concept of "persistent oxidative stress in cancer" and suggest a role of hMTH1 mRNA level as a prognostic marker.
Okamoto
K
K
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Japan.
Toyokuni
S
S
Kim
W J
WJ
Ogawa
O
O
Kakehi
Y
Y
Arao
S
S
Hiai
H
H
Yoshida
O
O
D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011519:Proto-Oncogenes; D011755:Pyrophosphatases; D012333:RNA, Messenger / Q000032:analysis*
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D012333:RNA, Messenger; C024829:8-hydroxyguanine; D006147:Guanine; D010744:Phosphoric Monoester Hydrolases; D011755:Pyrophosphatases; C052211:mutT protein, E coli