Cancer biomarkers in human atherosclerotic lesions: no evidence of p53 involvement.
In order to assess similarities between the atherogenic and the carcinogenic processes, we investigated whether the p53 tumor suppressor gene, the most commonly altered gene in human cancer, may be also involved in human atherosclerotic lesions. The medium layers of abdominal aorta fragments taken at surgery from 32 patients were subjected to immunohistochemical analysis, using either monoclonal (Pab 1801) or polyclonal (CM-1) antibodies, and to molecular analysis by the PCR-based denaturing gradient gel electrophoresis approach. The results obtained indicated that p53 mutations are not involved in the pathogenesis of atherosclerotic lesions, and that no accumulation of the wild-type protein occurs in smooth muscle cells of these lesions. A polymorphism characterized by an AT to GC transition at codon 213 (CGA --> CGG) causing no aminoacid substitution (Arg --> Arg) was detected in the 10.5% of the examined patients. Our negative findings do not support the hypothesis that the atherosclerotic plaques may be pathogenetically akin to benign tumors yet they are not in contrast with this theory, since in most cases p53 is involved in advanced stages of the carcinogenesis process.
D'Agostini
F
F
Institute of Hygiene and Preventive Medicine, University of Genoa, Italy.
Fronza
G
G
Campomenosi
P
P
Izzotti
A
A
Petrilli
G L
GL
Abbondandolo
A
A
De Flora
S
S
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001012:Aorta, Abdominal / Q000737:chemistry; D001018:Aortic Diseases / Q000235:genetics* / Q000378:metabolism*; D001120:Arginine; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D003062:Codon / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006147:Guanine; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D003062:Codon; D006147:Guanine; D001120:Arginine