title: Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions.
abstract: We generated replication-defective adenovirus Ad-p53AIP1 and studied its anti-tumor efficacy both in vitro and in vivo. We demonstrated that Ad-p53AIP1 infection elicited high levels of p53AIP1 expression in cancer cells. We also found that Ad-p53AIP1 expression induced marked apoptosis and cell cycle arrest in HepG2 cells. Moreover, Ad-p53AIP1 infection significantly inhibited the tumorigenesis of 4T1 mouse mammary cancer cells in vivo. In particular, we discovered that p53AIP1 overexpression up-regulated the protein levels of p53 in HepG2 cells, which was accompanied by down-regulation of MDM2 mRNA and protein, suggesting an interaction between MDM2 and p53 in p53AIP1-induced apoptosis and cell cycle arrest. Our data demonstrated the feasibility of Ad-p53AIP1-mediated cancer gene therapy. p53AIP1-induced up-regulation of p53 protein through MDM2 suggests that p53AIP1 gene therapy may be more advantageous in tumors expressing high levels of oncoprotein MDM2 or having a mutation in MDM2 inhibitor p16INK4.
authors.affiliation: Department of Pathobiology, Institute of Basic Medical Sciences, Beijing 100850,  P.R. China ;
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Jiang
authors.forename: Huihua
authors.initials: H
authors.lastname: Chen
authors.forename: Haiquan
authors.initials: H
authors.lastname: Jia
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Xu
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Yang
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Lu