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Transforming growth factor-β gene silencing using adenovirus expressing TGF-β1 or TGF-β2 shRNA

Authors
 S Oh  ;  E Kim  ;  D Kang  ;  M Kim  ;  J-H Kim  ;  J J Song 
Citation
 Cancer Gene Therapy, Vol.20(2) : 94-100, 2013 
Journal Title
 Cancer Gene Therapy 
ISSN
 0929-1903 
Issue Date
2013
Abstract
Tumor cells secrete a variety of cytokines to outgrow and evade host immune surveillance. In this context, transforming growth factor-β1 (TGF-β1) is an extremely interesting cytokine because it has biphasic effects in cancer cells and normal cells. TGF-β1 acts as a growth inhibitor in normal cells, whereas it promotes tumor growth and progression in tumor cells. Overexpression of TGF-β1 in tumor cells also provides additional oncogenic activities by circumventing the host immune surveillance. Therefore, this study ultimately aimed to test the hypothesis that suppression of TGF-β1 in tumor cells by RNA interference can have antitumorigenic effects. However, we demonstrated here that the interrelation between TGF-β isotypes should be carefully considered for the antitumor effect in addition to the selection of target sequences with highest efficacy. The target sequences were proven to be highly specific and effective for suppressing both TGF-β1 mRNA and protein expression in cells after infection with an adenovirus expressing TGF-β1 short hairpin RNA (shRNA). A single base pair change in the shRNA sequence completely abrogated the suppressive effect on TGF-β1. Surprisingly, the suppression of TGF-β1 induced TGF-β3 upregulation, and the suppression of TGF-β2 induced another unexpected downregulation of both TGF-β1 and TGF-β3. Taken together, this information may prove useful when considering the design for a novel cancer immunogene therapy.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86288
DOI
10.1038/cgt.2012.90
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
김주항(Kim, Joo Hang)
송재진(Song, Jae Jin)
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Full Text
http://www.nature.com/cgt/journal/v20/n2/full/cgt201290a.html
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