p53 point mutation in HPV negative human cervical carcinoma cell lines

Abstract

Clinical and experimental evidence is consistent with a key role for transforming human papilloma viruses (HPVs) in the aetiology of anogenital carcinoma. Cervical carcinoma does, however, occasionally occur in the absence of HPV sequences (Riou et al., 1990). We have used a direct cDNA/PCR sequencing protocol to analyse the sequence of p53 mRNA expressed by HPV positive and negative cervical carcinoma cell lines. Six cell lines which contain HPV sequences express p53 mRNA which has wild-type sequence throughout conserved boxes 2, 3, 4 and 5. The two HPV negative cell lines (C33a and HT3) express mutant p53 mRNA. In each case the mutation occurs in an evolutionarily conserved amino acid. Our data suggest that loss of wild-type p53 function is important in development of cervical carcinoma, and that this might be achieved either by mutation within the p53 gene or the presence of a virally encoded p53 binding protein.