title: Transforming growth factor-β gene silencing using adenovirus expressing TGF-β1 or TGF-β2 shRNA.
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.
authors.affiliation: Institute for Cancer Research, College of Medicine, Yonsei University, Seoul, South Korea.
authors.forename: S
authors.initials: S
authors.lastname: Oh
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Kang
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.forename: J J
authors.initials: JJ
authors.lastname: Song
mesh_terms: D000256:Adenoviridae; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D007165:Immunosuppression Therapy; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000627:therapeutic use; D053781:Transforming Growth Factor beta2 / Q000235:genetics* / Q000627:therapeutic use
chemical_list: D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2