Differential suppression of human cervical cancer cell growth by adenovirus delivery of p53 in vitro: arrest phase of cell cycle is dependent on cell line.
It has been reported that overexpression of wild-type p53 protein induces suppression of tumor cell growth in vivo and in vitro. In this study, we further evaluated the differential effects of p53 delivered in an adenovirus vector on the cell growth, apoptosis and cell cycle progression in cervical cancer cell lines. We constructed a recombinant adenovirus expressing p53 and then delivered this into cervical carcinoma cell lines (CaSki, SiHa, and HeLa, HeLaS3) along with adenovirus expressing beta-galactosidase as a negative control. Adenovirus-delivered p53 overexpression resulted in a more significant suppression of cell growth in HPV 18-infected cells (HeLa and HeLaS3) and a lesser suppression in HPV 16-infected cells (CaSki and SiHa). However, no suppression was observed in cells infected with a negative control virus. p53 overexpression also induced apoptosis and cell cycle arrest, as determined by annexin V and propidium iodide staining. In particular, the cell cycle was arrested in the G(2)/M phase in CaSki cells. In contrast, cell cycles were arrested in the G(1) phase in HeLa cells, suggesting that the arrest phase is dependent upon the cervical cancer cell line. Taken together, these data support the idea that overexpressed p53 protein plays a differential role in suppressing cervical cancer cell growth through apoptosis and cell cycle arrest in either G(1) or G(2)/M phase, depending on the cancer cell line.
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D005260:Female; D016158:Genes, p53; D015316:Genetic Therapy; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D012097:Repressor Proteins; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53