THE STATE OF P53 IN PRIMARY HUMAN CERVICAL CARCINOMAS AND ITS EFFECTSIN HUMAN PAPILLOMAVIRUS-IMMORTALIZED HUMAN CERVICAL CELLS

Wild-type (wt) p53 acts as a tumor suppressor, while certain mutant ty pe (mt) p53 may exhibit 'oncogenic' function. We have recently demonst rated that human papillomavirus type 18 (HPV-18) E6 can partially over come the growth-suppressive effects of wt p53, but it remains unclear what role p53 plays in cervical carcinogenesis. In this report, we hav e 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 ent ire p53-coding region of the two HPV-negative cervical cancers was seq uenced 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 (mtp43Val-135). The results indicate that HPV-immortalized cells cannot tolerate large amo unts of exogenous wt p53, while mt p53Val-135 can enhance transformati on of these cells. The results support the notion that inactivation of wt p53 by E6 may be important for HPV-associated transformation and a lso suggests that mt p53 can act as an oncogene in HPV-immoralized hum an cells.