Role of human papillomavirus and p53 tumor suppressor gene in cervical carcinogenesis.
To determine whether the dysfunction of p53 protein, caused either by the mutation of p53 gene itself or by the human papillomavirus (HPVs) is involved in the development of cervical cancers and to find out the status of p53 tumor suppressor gene in HPV positive or negative cancers, we analyzed 64 cases of primary cervix cancers. First, polymerase chain reaction (PCR) was performed with E6 consensus primer pairs to detect the infection of HPVs in cervix cancer tissues. Second, to screen the p53 gene mutation, PCR of p53 exon 5 through 9 and single strand conformation polymorphism (SSCP) analysis were performed with p53 exon specific primers. Finally, overexpression of p53 protein was checked by immunohistochemical staining with anti p53 antibody. We found HPVs in 43 cases out of 64 cases (67.2%). HPV type 16 was positive in 26 cases, type 18 was positive in 7 cases, and 6 cases were positive for both HPV type 16 and 18. HPV type 31 or 33 was not detected in our experiments, and in 4 cases, type of HPVs were unknown. The SSCP analysis showed mobility shifts in 8 cases (6 in HPV positive cases; 2 in HPV negative cases) and the sequence analysis confirmed the results of SSCP analysis. In addition, the overexpression suggesting the mutation of p53 gene was detected in 27 cases (42.2%, 21 in HPV positive cases; 6 cases in HPV negative cases). Our results support the previous reports that the dysfunction of p53 plays an important role in the development of cervix cancers but contrary to the results obtained from cervix cancer all lines, there is no inverse correlation between HPV infections and p53 mutations in primary cervix cancers.
Kim
K H
KH
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.
Kim
Y S
YS
D001483:Base Sequence; D005260:Female; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014412:Tumor Virus Infections; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000821:virology*