THE P53 TUMOR-SUPPRESSOR GENE IS OVEREXPRESSED BUT NOT MUTATED IN HUMAN ATHEROSCLEROTIC TISSUE

Excessive proliferation of smooth muscle cells (SMC) in the arterial i ntima is thought to be a major contributing factor to the development of atherosclerosis. One of the theories put forward to explain the abe rrant growth is that genetic alterations similar to those observed in cancers also occur in the SMC. Since mutations in the p53 tumour suppr essor gene and the c-Ki-ras oncogene are the most common genetic alter ations observed in a wide variety of tumour types, we searched for evi dence of mutation in human atherosclerotic tissue. DNA was extracted f rom atherosclerotic plaques and screened for p53 and c-Ki-ras gene mut ations using polymerase chain reaction-single strand conformation poly morphism analysis. Tissue sections were also examined for overexpressi on of p53 protein using an immunohistochemical technique. The molecula r analysis showed that wild-type p53 and c-Ki-ms gene sequences were p resent in all 54 specimens examined. Overexpression of p53 protein was found in 61% of samples. Our results do not support the view that gen etic alterations similar to those occurring in cancer contribute to th e abnormal proliferation of SMC, although we caution that only two can cer-related genes were studied. Epigenetic changes to the gene product s could play a role however, as evidenced by overexpression of p53 pro tein in many of the atherosclerotic specimens.