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

作者：Yin, Chunhua; Li, Jiaqi; He, Quan; Liu, Sisun; He, Linsheng^*

来源：International Journal of Clinical and Experimental Pathology, 2017, 10(4): 4356-4362.

• Cervical cancer
• p53
• HPV-negative
• chemo-resistance
• nucleotide salvage

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.

• 出版日期2017
• 单位南昌大学