title: The p53 tumor-suppressor gene is overexpressed but not mutated in human atherosclerotic tissue.
abstract: Excessive proliferation of smooth muscle cells (SMC) in the arterial intima is thought to be a major contributing factor to the development of atherosclerosis. One of the theories put forward to explain the aberrant growth is that genetic alterations similar to those observed in cancers also occur in the SMC. Since mutations in the p53 tumour suppressor gene and the c-Ki-ras oncogene are the most common genetic alterations observed in a wide variety of tumour types, we searched for evidence of mutation in human atherosclerotic tissue. DNA was extracted from atherosclerotic plaques and screened for p53 and c-Ki-ras gene mutations using polymerase chain reaction-single strand conformation polymorphism analysis. Tissue sections were also examined for overexpression of p53 protein using an immunohistochemical technique. The molecular analysis showed that wild-type p53 and c-Ki-ms gene sequences were present in all 54 specimens examined. Overexpression of p53 protein was found in 61% of samples. Our results do not support the view that genetic alterations similar to those occurring in cancer contribute to the abnormal proliferation of SMC, although we caution that only two cancer-related genes were studied. Epigenetic changes to the gene products could play a role however, as evidenced by overexpression of p53 protein in many of the atherosclerotic specimens.
authors.forename: B
authors.initials: B
authors.lastname: Iacopetta
authors.forename: S
authors.initials: S
authors.lastname: Wysocki
authors.forename: P
authors.initials: P
authors.lastname: Norman
authors.forename: A
authors.initials: A
authors.lastname: House