Abstract

Here, the carcinogenicity between the wild type and mutant human papillomavirus 58 E7 in cervical cancer was compared both in vitro and in vivo. Keratinocyte cell line HaCaT and human papillomavirus negative cervical cancer cell line C33A cells stably expressing wild type human papillomavirus 58 E7 (WT) or human papillomavirus 58 E7 variant (T20I/G63S, MT) were constructed by using lentivirus system. Through a series of phenotypic tests, such as wound healing assay, Transwell experiment, 3-(4,5-dimethyl- 2-thia-zolyl)-2,5-diphenyl-2-H-tetrazolium bromide method, flow cytometry, colony formation assay, we initially explored the carcinogenicity differences of human papillomavirus 58 E7 variants in vitro. The role of two types of human papillomavirus 58 E7 on cervical cancer cell growth in vivo was examined using nude mouse xenograft model and the terminal deoxynucleotidyl transferase dUTP nick end labeling staining was performed to measure the cell apoptosis in tumors. Our results showed that both keratinocyte cell line HaCaT and human papillomavirus negative cervical cancer cell line C33A cells with overexpressed variant human papillomavirus 58 E7 (T20I/G63S, MT) presented stronger migration and invasion potential and stronger proliferation and colony formation activity and much low cell apoptosis rates compared with the corresponding wild type group cells. The results from animal experiment revealed that xenografts from human papillomavirus negative cervical cancer cell line C33A cells overexpressed variant human papillomavirus 58 E7 (T20I/G63S, MT) grow much quickly and less cells were under apoptosis. We identified the human papillomavirus 58 E7 (T20I/G63S, MT) variants which possessed higher carcinogenicity on cervix than the wild type one.