IFNγ-mediated inhibition of cell proliferation through increased PKCδ-induced overexpression of EC-SOD

BMB Reports

Yoon-Jae Jeon^1¹  Hyun Yoo^1² 

[1] Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul 137-040^1;Department of New Drug Discovery and Development New Drug Development, Chungnam National University, Daejeon 305-764, Korea^2

关键词: EC-SOD;   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

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.

【 授权许可】

Unknown