Phospholipase Cε as a potential molecular target for anti-inflammatory therapy and cancer prevention

• Edamatsu Hironori

  Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

• Takenaka Nobuyuki

  Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

• Hu Lizhi

  Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

• Kataoka Tohru

  Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

抄録

Phospholipase Cε (PLCε), encoded by PLCE1, is the phosphoinositide-specific PLC regulated by the ras proto-oncogene product Ras and its relative Rap1. Like other PLC isoforms, PLCε catalyzes hydrolysis of phosphatidylinositol 4,5-bisphosphate to yield second messengers, diacylglycerol and inositol 1,4,5-trisphosphate. To understand the physiological function of PLCε, we have created and analyzed genetically-modified mice in which PLCε is inactivated or overproduced. PLCε knockout (KO) mice are resistant to two-stage skin chemical carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene and promoted by phorbol 12-myristate 13-acetate (PMA) and to intestinal tumorigenesis caused by the loss-of-function mutation of the APC tumor suppressor gene. In PLCε KO mice, inflammation, such as that induced by a single application of PMA, that associated with tumorigenesis, and that in the elicitation phase of allergic contact hypersensitivity, is also attenuated as compared to that in wild-type mice. Conversely, overexpression of PLCε in the epidermis results in the development of skin inflammation that partly shares the features with human psoriasis. In this article, we summarize the data showing the role of PLCε in tumorigenesis and inflammation and discuss the future directions of the study of PLCε for the development of therapies to control inflammation and to prevent cancer progression.

収録刊行物

• Inflammation and Regeneration

  Inflammation and Regeneration 31 (4), 370-374, 2011

  一般社団法人 日本炎症・再生医学会

キーワード

• inflammatory cytokines
• mouse models
• non-immune cells
• psoriasis
• tumorigenesis

詳細情報

• CRID: 1390282680233543680
• NII論文ID: 130004482284
• DOI: 10.2492/inflammregen.31.370
• ISSN: 18808190
• ISSN: 18809693
• Web Site: https://search.jamas.or.jp/link/ui/2012162646
• 本文言語コード: en
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• 抄録ライセンスフラグ: 使用不可