Functional characterization of p53 molecules expressed in human squamous cell carcinomas of the head and neck

摘要: Mutation of the p53 tumor suppressor gene has been demonstrated in a large proportion human head and neck squamous cell carcinomas (HNSCCs) assumed to play role pathogenesis these tumors, although no formal evidence functional aberration demonstrated. In this study, we isolated cDNA clones encoding entire coding region from six HNSCC lines that showed aberrant patterns expression parental cells, analyzed their nucleotide sequences, characterized function vivo. cDNAs cloned four harbored alterations within sequence (one missense mutation, one mutation plus in-frame deletion, splice donor 1-nt insertion). HN30 which contained wild-type high constitutive level protein expression. HN26 cells sequences but did not express 53-kDa protein, mRNA was transcribed molecule increased molecular mass (70 kDa) observed by western blotting. Functional studies revealed none proteins encoded mutant were able transactivate reporter plasmid containing consensus binding site when cotransfected into p53-null whereas molecules about hundredfold over uninduced levels. Co-expression each with p53-responsive some degree inhibitory activity varied depending on present. Thus, as result or altered characterizes oral carcinomas. The may be mechanism for deregulation co-expressed importance during early stages development. Mol. Carcinog. 18:89–96, 1997. © 1997 Wiley-Liss, Inc.