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

Yoon-Jae Jeon; Hyun Yoo; Byung Hak Kim; Yun Sang Lee; Byeongwook Jeon; Sung-Sub Kim; Tae-Yoon Kim

doi:10.5483/bmbrep.2012.45.11.003

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

BMB Rep. 2012 Nov;45(11):659-64. doi: 10.5483/bmbrep.2012.45.11.003.

Authors

Yoon-Jae Jeon¹, Hyun Yoo, Byung Hak Kim, Yun Sang Lee, Byeongwook Jeon, Sung-Sub Kim, Tae-Yoon Kim

Affiliation

¹ Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / pharmacology
Blotting, Western
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
Cell Proliferation / drug effects*
Cells, Cultured
Gene Expression Regulation, Enzymologic / drug effects*
Humans
Interferon-gamma / pharmacology*
Keratinocytes / drug effects
Keratinocytes / metabolism
Keratinocytes / pathology
Melanoma / drug therapy
Melanoma / metabolism
Melanoma / pathology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Protein Kinase C-delta / metabolism*
RNA, Small Interfering / genetics
Reactive Oxygen Species / metabolism
Skin Neoplasms / drug therapy
Skin Neoplasms / metabolism
Skin Neoplasms / pathology*
Superoxide Dismutase / antagonists & inhibitors
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism*
Up-Regulation

Substances

Antiviral Agents
RNA, Small Interfering
Reactive Oxygen Species
Interferon-gamma
Sod3 protein, mouse
Superoxide Dismutase
Protein Kinase C-delta