The state of p53 in primary human cervical carcinomas and its effects in human papillomavirus-immortalized human cervical cells

Oncogene. 1993 Jun;8(6):1511-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Division
  • Cell Line
  • Cell Line, Transformed
  • Cell Transformation, Viral
  • Cervix Uteri / cytology
  • Cervix Uteri / microbiology
  • DNA-Binding Proteins*
  • Female
  • Genes, p53*
  • Humans
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Oncogene Proteins, Viral / analysis
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Papillomaviridae / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology


  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 18
  • Oligodeoxyribonucleotides
  • Oncogene Proteins, Viral
  • Tumor Suppressor Protein p53