Concomitant loss of mitochondria and the DNA repair protein hOGG1 in clear cell carcinoma of the kidney.
The kidney is subjected to DNA oxidative damage from reactive oxygen species generated by free radicals and toxic metabolites, leading to formation of DNA base lesions. One such DNA lesion is 8-oxoguanine, which, if not sufficiently removed, is potentially mutagenic because it can cause G:C to T:A transversion in subsequent DNA replication. The human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene on chromosome 3, a region (3p25-26) that shows frequent loss of heterozygosity in clear cell renal cell carcinoma (CC-RCC), encodes for a DNA repair enzyme capable of excision repair of 8-oxoguanine. Of the known isoforms of the hOGG1 enzyme (types Ia, Ib, Ic, Id, and II), only 1, Ia, is found in the nucleus, whereas the rest show a mitochondrial distribution. We investigated, by an immunohistochemical staining method, the expression of hOGG1 protein in 40 cases of CC-RCC, using archival formalin-fixed tissue. To localize the hOGG1 enzyme in normal and tumor tissue, immuno-staining against cytochrome c, a specific mitochondrial enzyme, was also performed. The results showed marked reduction in hOGG1 expression in the majority of tumors, with complete loss of staining seen in 26 (65%) and moderate and weak positive staining present in 9 (22.5%) and 5 (12.5%) of the cases, respectively. Strong hOGG1 protein expression was present in normal tubular epithelium, located in the mitochondria. The results correlated with the expression patterns of cytochrome c. The findings indicate that loss of hOGG1 expression may have a role in development or progression of CC-RCC.
Mukunyadzi
Perkins
P
Department of Pathology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, U.S.A. mukunyadziperkins@uams.edu
Huang
Huaiyun
H
Liu
Kela
K
Fan
Chun-Yang
CY
D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D045304:Cytochromes c / Q000032:analysis; D045647:DNA Glycosylases / Q000032:analysis*; D004260:DNA Repair / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D008928:Mitochondria / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000032:analysis
D007527:Isoenzymes; D024101:Mitochondrial Proteins; D045304:Cytochromes c; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human