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

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.