IGFBP7は,B-RAF誘発のメラノサイト老化には必要ありません
Lyndee L Scurr1, Gulietta M Pupo, Therese M Becker
1Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales 2145, Australia. lyndee_scurr@wmi.usyd.edu.au
Cell
|May 19, 2010
まとめ
インスリン類似成長因子結合タンパク質7 (IGFBP7) は,ヒトメラノサイトにおける腫瘍性B-RAF誘発の衰老に欠かせない. この研究は,B-RAFシグナル伝達とIGFBP7発現との間に関連性がないことを発見し,以前の発見に異議を唱えました.
科学分野:
- 腫瘍学 腫瘍学
- 細胞生物学 細胞生物学
- 分子医学は分子医学である.
背景:
- 細胞老化は,腫瘍性刺激後の増殖を停止することによって,腫瘍抑制剤として作用する.
- インスリン類似成長因子結合タンパク質7 (IGFBP7) は,以前,腫瘍性B-RAF誘発のメラノサイト衰老の媒介者として提案されていた.
- 腫瘍性B-RAF変異は,皮膚性ネビやメラノーマで一般的です.
研究 の 目的:
- 人間のメラノサイトにおけるB-RAF誘発の衰老におけるIGFBP7の役割を調査する.
- B-RAFシグナル伝達とIGFBP7発現と,その下流目標との関連性を再評価する.
- 腫瘍性B-RAFによる衰老誘発にIGFBP7が不可欠であるかどうかを判断する.
主な方法:
- IGFBP7とその標的遺伝子発現 (BNIP3L,SMARCB1,PEA15) をヒトのメラノ細胞と線維芽細胞で定量分析した.
- B-RAFの変異状態と,メラノーマ細胞系,メラノーマ,良性腫瘍におけるIGFBP7タンパク質レベルとの相関分析.
- IGFBP7のレンチウイルス性遺伝子静止は,B-RAF誘発の衰老のためにその必要性を評価する.
主要な成果:
- B-RAFシグナリングは,ヒトメラノサイトまたは線維芽細胞におけるIGFBP7発現またはその提案された標的遺伝子を誘導しませんでした.
- 様々な臨床サンプルで,B-RAF変異状態とIGFBP7タンパク質濃度との間には相関は見られなかった.
- IGFBP7を静止することは,B-RAFがメラノサイトと線維芽細胞の衰老を誘発することを防ぐことはできませんでした.
結論:
- 分泌されるタンパク質IGFBP7は,ヒトメラノ細胞におけるB-RAF (V600E) 誘発の衰老に欠かせない.
- IGFBP7がB-RAF誘発の衰老を媒介することを示唆する以前の発見は,再評価を必要とする.
- 腫瘍性B-RAFによる老化誘発は,これらの細胞モデルにおいてIGFBP7とは独立して発生する.
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