Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions

Jiang,Yunbo; Chen,Huihua; Jia,Haiquan; Xu,Yuanji; Liu,Gang; Wang,Yan; Yang,Xiaohe; Lu,Yinglin

doi:10.3892/etm_00000057

March-April 2010 Volume 1 Issue 2

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March-April 2010 Volume 1 Issue 2

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Article

Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions

Authors:
- Yunbo Jiang
- Huihua Chen
- Haiquan Jia
- Yuanji Xu
- Gang Liu
- Yan Wang
- Xiaohe Yang
- Yinglin Lu
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Affiliations: Department of Pathobiology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China
Pages: 363-368
|
Published online on: March 1, 2010

https://doi.org/10.3892/etm_00000057
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions

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