The state of p53 in primary human cervical carcinomas and its effects in human papillomavirus-immortalized human cervical cells.
Wild-type (wt) p53 acts as a tumor suppressor, while certain mutant type (mt) p53 may exhibit 'oncogenic' function. We have recently demonstrated that human papillomavirus type 18 (HPV-18) E6 can partially overcome the growth-suppressive effects of wt p53, but it remains unclear what role p53 plays in cervical carcinogenesis. In this report, we have examined nine HPV-immortalized human cervical epithelial cell lines and 13 HPV-positive and two HPV-negative primary cervical cancers for p53 mutations by polymerase chain reaction--single-strand conformation polymorphism (PCR-SSCP). None of them contained p53 mutations in exons 5-9 where most p53 mutations in human tumors have been found. The entire p53-coding region of the two HPV-negative cervical cancers was sequenced and no mutations were noted. In order to examine the effects of wt p53 and mt p53 on HPV-immortalized human cells, we transfected HPV-immortalized cell lines with wt p53 and a mt p53 (mtp53Val-135). The results indicate that HPV-immortalized cells cannot tolerate large amounts of exogenous wt p53, while mt p53Val-135 can enhance transformation of these cells. The results support the notion that inactivation of wt p53 by E6 may be important for HPV-associated transformation and also suggests that mt p53 can act as an oncogene in HPV-immoralized human cells.
Department of Pathology, New York University Medical Center, New York 10016.
T M
TM
Chen
C A
CA
Chen
C Y
CY
Hsieh
D Y
DY
Chang
Y H
YH
Chen
V
V
Defendi
D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002584:Cervix Uteri / Q000166:cytology / Q000382:microbiology; D004268:DNA-Binding Proteins; D005260:Female; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D016159:Tumor Suppressor Protein p53