Gene therapy for cancer through adenovirus vector‑mediated expression of the Ad5 early region gene 1A based on loss of IGF2 imprinting

Pan,Yuqin; He,Bangshun; Lirong,Zhang; Nie,Zhenlin; Chen,Liping; Gu,Ling; Hoffman,Andrew   R.; Wang,Shukui; Hu,Jifan

doi:10.3892/or.2013.2646

October 2013 Volume 30 Issue 4

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October 2013 Volume 30 Issue 4

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Article

Gene therapy for cancer through adenovirus vector‑mediated expression of the Ad5 early region gene 1A based on loss of IGF2 imprinting

Authors:
- Yuqin Pan
- Bangshun He
- Zhang Lirong
- Zhenlin Nie
- Liping Chen
- Ling Gu
- Andrew R. Hoffman
- Shukui Wang
- Jifan Hu
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Affiliations: Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210012, P.R. China, Department of Medicine, Stanford University Medical School, Palo Alto, CA 94304, USA, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA
Pages: 1814-1822
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Published online on: July 30, 2013

https://doi.org/10.3892/or.2013.2646
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Abstract

Loss of (genomic) imprinting (LOI) of the insulin-like growth factor 2 gene (IGF2) is a common epigenetic abnormality in many human cancers. IGF2 imprinting is regulated by differentially methylated domains (DMD) in the imprinting control region that is located between IGF2 and H19 on human chromosome 11. In the present study, combined expression of adenoviral vectors (Ad-EGFP and Ad-E1A) driven by H19 enhancer-DMD-H19 promoter complex was investigated and their effects on the tumor growth were assessed in vitro and in vivo. When infected with Ad-EGFP, the cancer cell lines with the LOI, such as HRT-18 and HT-29 cells, had the expression of the EGFP protein, whereas three cancer cell lines with the maintenance of imprinting (MOI) (HCT-116, MCF-7 and GES-1) had weak expression of EGFP. Furthermore, the expressed Ad-E1A significantly decreased cell viability and induced cell apoptosis only in HRT-18 and HT-29 cells in vitro, and effectively suppressed tumor development in HRT-18 and HT-29 xenograft in nude mice. It is concluded that this gene therapy vector is effective in the suppression of the growth of human colon cancer cells in vitro and in vivo, and that cancer gene therapy based on loss of IGF2 imprinting may prove to be a novel therapeutic option.

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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

Gene therapy for cancer through adenovirus vector‑mediated expression of the Ad5 early region gene 1A based on loss of IGF2 imprinting

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