開発クロマチンのプログラムは,メラノーマにおける腫瘍性能力を決定する.
Arianna Baggiolini1, Scott J Callahan1,2,3, Emily Montal2
1Center for Stem Cell Biology and Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
まとめ
腫瘍遺伝子は特定の文脈でのみ細胞を変容させ 腫瘍遺伝能力として知られています この研究では,ATAD2のような 発達性クロマチンの要因が 腫瘍遺伝子に対する細胞の反応を調節し,癌の発生に影響を及ぼすことが明らかになりました.
科学分野:
- 癌 生物学
- 発達生物学
- 遺伝学
背景:
- 腫瘍遺伝子は細胞を変化させることができますが この能力は文脈に依存し 腫瘍遺伝能力と呼ばれる現象です
- 腫瘍性能力を与える細胞因子を理解することは,がん研究にとって極めて重要です.
研究 の 目的:
- 細胞の内在的な転写プログラムが 腫瘍性能力の調停に 果たす役割を調査する.
- 腫瘍性変異に対する細胞の反応を調節する特定の要因を特定する.
主な方法:
- ヒトの多能幹細胞を 癌モデルとして利用した
- 腫瘍遺伝子による変異を研究するためにゼブラフィッシュの変異を採用した.
- 重要な調節因子を特定するために遺伝子発現プロファイリングを行いました.
主要な成果:
- BRAFV600Eや他の突然変異の変換能力は,発生細胞の転写プログラムに依存しています.
- ニューラル・クライストとメラノブラストの集団と比較して,メラノサイトは腫瘍性変異に反応しやすい.
- プロジェニータ細胞は,メラノーマの重要な能力因子であるATAD2を含むクロマチンの修飾酵素のより高い発現を示します.
結論:
- 腫瘍遺伝子の能力は,腫瘍遺伝子に対する細胞の反応を調節する発達性染色体因子によって媒介される.
- ATAD2はSOX10と相互作用し,下流の腫瘍性およびニューラル・クライストプログラムの発現を可能にします.
- これらの発見は,がんの発症における発達状況の重要性を強調しています.
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