title: Gene therapy for cancer through adenovirus vector‑mediated expression of the Ad5 early region gene 1A based on loss of IGF2 imprinting.
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.
authors.affiliation: Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210012, P.R. China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Pan
authors.forename: Bangshun
authors.initials: B
authors.lastname: He
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lirong
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Nie
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Gu
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: Shukui
authors.initials: S
authors.lastname: Wang
authors.forename: Jifan
authors.initials: J
authors.lastname: Hu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D019175:DNA Methylation / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D045325:HCT116 Cells; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D017500:Adenovirus E1A Proteins; C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007335:Insulin-Like Growth Factor II
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