Alterations of the p53 tumor suppressor gene during mouse skin tumor progression.

摘要: Abstract The two-stage murine skin tumorigenesis model is widely used to study the development of squamous cell neoplasias. We have investigated expression p53 and retinoblastoma tumor suppressor genes in eight lines varied histopathology malignant potential, seven vivo-derived clones from these lines, 39 primary short-term cultures similarly induced tumors at various stages progression. One carcinoma line three more derived it revealed mutations protein by immunoprecipitation analyses despite normal-sized transcripts. Sequence analysis identified nature point a G→C transversion codon 132. Mouse transcripts were unaltered all examined. Among tumors, gene appeared normal papillomas early well-differentiated carcinomas Southern analyses. In contrast, four later promotion (50–60 weeks) possessed alterations p53, including loss product, immunoreactivity with murine-specific antibody recognizing only wild-type protein. Loss heterozygosity locus was observed several promotion. contrast regardless stage or histological grade tumor. Direct sequence exons 5 through 8 advanced 25% incidence mutations. These located codons 245 263. Collectively, data indicate that occur 25 50% protocol are events Moreover, associated possessing and/or poorly differentiated phenotype.