title: IFNγ-mediated inhibition of cell proliferation through increased PKCδ-induced overexpression of EC-SOD.
abstract: Extracellular superoxide dismutase (EC-SOD) overexpression modulates cellular responses such as tumor cell suppression and is induced by IFNγ. Therefore, we examined the role of EC-SOD in IFNγ-mediated tumor cell suppression. We observed that the dominant-negative protein kinase C delta (PKCδ) suppresses IFNγ-induced EC-SOD expression in both keratinocytes and melanoma cells. Our results also showed that PKCδ-induced ECSOD expression was reduced by pretreatment with a PKCspecific inhibitor or a siRNA against PKCδ. PKCδ-induced ECSOD expression suppressed cell proliferations by the up-regulation of p21 and Rb, and the downregulation of cyclin A and D. Finally, we demonstrated that increased expression of EC-SOD drastically suppressed lung melanoma proliferation in an EC-SOD transgenic mouse via p21 expression. In summary, our findings suggest that IFNγ-induced EC-SOD expression occurs via activation of PKCδ. Therefore, the upregulation of EC-SOD may be effective for prevention of various cancers, including melanoma, via cell cycle arrest.
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea.
authors.forename: Yoon-Jae
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Hyun
authors.initials: H
authors.lastname: Yoo
authors.forename: Byung Hak
authors.initials: BH
authors.lastname: Kim
authors.forename: Yun Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Byeongwook
authors.initials: B
authors.lastname: Jeon
authors.forename: Sung-Sub
authors.initials: SS
authors.lastname: Kim
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051745:Protein Kinase C-delta / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000998:Antiviral Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D007371:Interferon-gamma; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D051745:Protein Kinase C-delta