WT1媒介による,WT1スプライシング変種を発現するウィルムズ腫瘍細胞の成長抑制

D A Haber¹, S Park, S Maheswaran

¹Laboratory of Molecular Genetics, Massachusetts General Hospital Cancer Center, Boston 02129.

Science (New York, N.Y.)

|December 24, 1993

まとめ

研究者らは,ヒトのウィルムズ腫瘍細胞系で腫瘍抑制剤WT1 (ウィルムズ腫瘍1) をテストした. 彼らは,腫瘍細胞の特定のWT1遺伝子変異を発見し,ウィルムズ腫瘍発達の新たなメカニズムを示唆した.

科学分野:

分子生物学は分子生物学である.
遺伝学遺伝学とは
腫瘍学腫瘍学

背景:

ウィルムズ腫瘍は小児性腎臓がんである.
WT1 (ウィルムズ腫瘍1) は,腎臓の発達に不可欠な遺伝子です.
WT1の変異は,ウィルムズ腫瘍の発達と関連しています.

研究の目的:

WT1.1.の腫瘍抑制活性を調べるために.
ウィルムズ腫瘍細胞におけるWT1遺伝子発現を分析する.

主な方法:

ヒトのウィルムズ腫瘍細胞系 (RM1) を開発した.
感染したRM1細胞に,野生型のWT1同型体がある.
腫瘍細胞と正常な腎臓組織におけるWT1トランスクリプトスプライシングを分析した.

主要な成果:

WT1イソフォームは,RM1細胞の成長を抑制しました.
RM1細胞の内生的なWT1トランスクリプトに,特定のスプライシング変異 (エクソン2欠落) が発見されました.
この変異は,試験されたすべてのウィルムズ腫瘍に異なった量で存在したが,正常な腎臓組織には存在しなかった.

結論:

特定されたWT1スプライシング変異は,機能的に変化したタンパク質を生成します.
この異常なトランスクリプトは,ウィルムズ腫瘍におけるWT1不活性化のための新しいメカニズムを表す可能性があります.

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