Mutations and reduced expression of p53 gene are involved in HPV-independent oncogenesis of cervical cancer

Cervical cancer is one of the most prevalent malignancies in women, which has human papillomavirus infection as the major risk factor. Here we report the establishment of a new HPV-negative cervical cancer cell line and characterization of genetic alterations relevant to the pathogenesis of cervical cancer. A new cervical cancer cell line was established by extensive culture and natural selection of cells a cervical cancer sample of a 53-year woman. Human papillomavirus was detected by ELISA and PCR. The expression levels of p53 and k-ras were analyzed by immunocytochemical staining, the mutations of p53 and k-ras were assessed by PCR-sequencing, the sensitivity to cisplatin and taxol was measured by MTT assay, chromosomal anomaly was detected by karyotyping. The newly established cervical cancer cell line (CTCC-1) did not have detectable HPV DNA or HPV viral particle. CTCC-1 cells had massive chromosomal changes and harbored heterozygous mutations at 870 C>T (protein Pro223Leu) and 1022 G>T (protein Val274Phe) of p53 gene (NM_000546) with reduced p53 expression compared to C33A cells whereas k-ras was not mutated nor inhibited in CTCC-1 cells. CTCC-1 cells were more sensitive to cisplatin and taxol than Hela but more resistant to taxol than C33A cells. Overexpressing wild type p53 significantly increased the sensitivity of CTCC-1 to those chemotherapy agents. Mutant p53 might be responsible for the oncogenesis of some HPV-negative cervical cancers.