Adenovirus-mediated p53 gene transfer inhibits growth of human tumor cells expressing mutant p53 protein.

摘要: Human malignancies are often characterized by mutations of the p53 tumor suppressor gene. In a large proportion cases, mutation results in production an altered protein that can bind and inactivate wild-type gene product. This "dominant-negative" activity mutant molecules may limit utility therapy cancer. Using replication-deficient recombinant adenoviruses (rAd-p53) as delivery system, we evaluated effects reintroduction on series 45 human cell lines containing wild-type, mutated, or no protein. Results indicate p53-specific, dose-dependent, promoter-specific growth inhibition majority p53-altered correlates with degree adenovirus transgene expression. Similar were not observed cells p53. rAd-p53 inhibited expressing various proteins including those "dominant negative mutants", antiproliferative abrogated high levels endogenous mutated vivo, also suppressed increased survival nude mice bearing tumors express These support role for cancer, harboring this