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

• Main Author: Yoon-Jae Jeon1, Hyun Yoo1, Byung Hak Kim1, Yun Sang Lee1, Byeongwook Jeon1, Sung-Sub Kim2,* & Tae-Yoon Kim1,*
• Format: Article
• Language: English
• Published: Korean Society for Biochemistry and Molecular Biology 2012-11-01
• Series: BMB Reports
• Subjects: EC-SOD; IFNγ; Keratinocytes; Melanoma; PKCδ
• Online Access: http://www.jbmb.or.kr/jbmb/pdf.php?data=MTMwMTIyMTZAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS0xMSU1RDEyMTEyOTEzNThfJTI4NjU5LTY2NCUyOUJNQl8xMi0wMDMucGRm
• ISSN: 1976-6696; 1976-670X

Extracellular superoxide dismutase (EC-SOD) overexpressionmodulates cellular responses such as tumor cell suppression andis induced by IFNγ. Therefore, we examined the role of EC-SODin IFNγ-mediated tumor cell suppression. We observed that thedominant-negative protein kinase C delta (PKCδ) suppressesIFNγ-induced EC-SOD expression in both keratinocytes andmelanoma cells. Our results also showed that PKCδ-induced ECSODexpression was reduced by pretreatment with a PKCspecificinhibitor or a siRNA against PKCδ. PKCδ-induced ECSODexpression suppressed cell proliferations by the up-regulationof p21 and Rb, and the downregulation of cyclin A and D.Finally, we demonstrated that increased expression of EC-SODdrastically suppressed lung melanoma proliferation in an EC-SODtransgenic mouse via p21 expression. In summary, our findingssuggest that IFNγ-induced EC-SOD expression occurs via activationof PKCδ. Therefore, the upregulation of EC-SOD may beeffective for prevention of various cancers, including melanoma,via cell cycle arrest.