Expression of human MutT homologue (hMTH1) protein in primary non-small-cell lung carcinomas and histologically normal surrounding tissue.
In situ, oxidation of deoxyguanosine yields 8-hydroxy-2'-deoxyguanosine (8-oxo-dG), which is mutation prone and results in a G:C --> T:A transversion following DNA replication. Another pathway to the formation of DNA containing 8-oxo-dG is by the misincorporation of 8-oxo-dGTP via DNA polymerase. Human MutT homologue (hMTH1), an 8-oxo-dGTPase, prevents misincorporation of this oxidized nucleotide by hydrolyzing 8-oxo-dGTP to 8-oxo-dGMP. Previous studies have shown that hMTH1 mRNA is overexpressed in human renal cell carcinomas and breast tumors. Elevated levels of hMTH1 protein have also been detected in brain tumors. In the current study, we determined whether hMTH1 protein is overexpressed in primary non-small-cell lung carcinomas as compared to adjacent histologically normal lung tissue. Twenty matched human lung tumor/normal pairs were examined by Western analysis for expression of hMTH1 protein. Overexpression in the tumors was detected in 4/8 (50%) adenocarcinomas, 4/4 (100%) adenocarcinomas with bronchioalveolar (BAC) features, 2/2 (100%) BACs, and 3/6 (50%) squamous cell carcinomas. The data from Western analysis were validated by immunohistochemical staining for hMTH1 protein. The results of this study indicate that hMTH1 protein may be a potential marker for the detection of persistent oxidative stress in lung cancer.
Kennedy
Christopher H
CH
Cancer Prevention Fellowship Program, Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute/NIH, 10 Center Drive, Building 10, Bethesda, MD 20892-1002, USA. kennedch2@mail.nih.gov
Pass
Harvey I
HI
Mitchell
James B
JB
D000230:Adenocarcinoma / Q000201:enzymology*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D016022:Case-Control Studies; D045643:DNA Repair Enzymes; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases
D014408:Biomarkers, Tumor; D029968:Escherichia coli Proteins; D009363:Neoplasm Proteins; D010744:Phosphoric Monoester Hydrolases; D011755:Pyrophosphatases; C052211:mutT protein, E coli; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes