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: Yoon-Jae Jeon, Hyun Yoo, Byung Hak Kim, Yun Sang Lee, Byeongwook Jeon, Sung-Sub Kim, Tae-Yoon Kim
• Journal: BMB reports (BMB Rep) Vol. 45 Issue 11 Pg. 659-64 (Nov 2012) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 23187006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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