B細胞リンパ腫におけるA20の頻繁な不活性化
Motohiro Kato1, Masashi Sanada, Itaru Kato
1Cancer Genomics Project, Department of Pediatrics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Nature
|May 5, 2009
まとめ
A20タンパク質の喪失はB細胞リンパ腫では一般的であり,制御不能なNF-kappaBシグナル伝達と腫瘍の成長を促します. A20の機能を回復すると,リンパ腫の発症とNF-kappaBの活性化が抑制されます.
科学分野:
- 腫瘍学 腫瘍学
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
背景:
- A20 (TNFAIP3) は,免疫反応に不可欠なNF-kappaB経路を否定的に調節する.
- A20の遺伝的変異は,自己免疫疾患と関連しています.
- 人間の癌発症におけるA20の役割は,ほとんど知られていなかった.
研究 の 目的:
- B系統リンパ腫の病原性におけるA20の関与を調査する.
- A20 がリンパ腫における頻繁な遺伝的標的であるかどうかを判断する.
主な方法:
- 238個のB細胞リンパ腫のサンプルにおける遺伝的病変の全ゲノム分析.
- リンパ腫細胞系における野生型および変異性A20の再発現を含む機能的研究.
- 免疫不全マウスの腫瘍起源性アッセイ.
主要な成果:
- A20は,粘膜関連組織リンパ腫 (21.8%) と結節性硬化症ホジキンリンパ腫 (33.3%) の変異/消去によって頻繁に不活性化されます.
- 野生型A20抑制リンパ腫細胞の成長,誘発アポトーシス,および下調調節されたNF-kappaB活性化の再発.
- A20欠乏細胞はマウスで腫瘍を形成し,A20再発現によって抑制された.
結論:
- A20機能の喪失は,制御不能なNF-kappaBシグナル伝達によってB系統リンパ腫の発生に寄与する.
- A20は,特定のB細胞リンパ腫の腫瘍抑制剤として作用します.
- NF-kappaBを標的とする治療戦略は,A20欠乏性リンパ腫に有益である可能性があります.
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