細胞癌化とその抑制における転写因子の役割

2004 Fiscal Year Annual Research Report

• Project/Area Number: 15027201
• Research Institution: University of Tsukuba
• Principal Investigator: 山本 雅之 筑波大学, 大学院・人間総合科学研究科, 教授 (50166823)
• Co-Investigator(Kenkyū-buntansha): 大根田 絹子 筑波大学, 大学院・人間総合科学研究科, 講師 (50323291) ; 清水 律子 筑波大学, 大学院・人間総合科学研究科, 講師 (40226262)
• Keywords: GATA-1 / GATA-2 / 白血病 / 造血 / トランスジェニックマウス

Research Abstract

本研究は、赤血球の増殖・分化・アポトーシスの制御とその破綻がもたらす造血器腫瘍の形成過程において、GATA転写因子が果たす役割を解明することを目的としている。私たちは本研究を通して、GATA-1遺伝子ノックダウンマウスヘテロ接合体に発症する白血病細胞においてGATA-2の発現が亢進していることを見出した。また、GATA-2遺伝子の血球特異的なプロモーター下流に緑色蛍光蛋白質(GFP)遺伝子を挿入したマウスを解析した結果、GATA-2を発現する細胞は高い割合でS/G2/M期の細胞を含み、細胞増殖関連遺伝子を多く発現する増殖性の高い細胞であることを明らかにした。さらに、GATA-1遺伝子の血球特異的発現制御領域(G1-HRD)の下流にGFP遺伝子を挿入したマウスの解析の結果、GATA-1遺伝子の発現は赤血球の分化段階に応じて著しく変動し、その発現が最も高いのはCFU-Eから前赤芽球を含むLin^-/c-kit^+/CD71^+分画(Late erythroid progenitor)であることを発見した。このようなGATA-1とGATA-2の発現プロファイルの相違はそれぞれのGATA因子の細胞増殖、分化、癌発症における役割を解析するうえで重要な手がかりとなる。今年度はさらに、生体用ルミノメーターとルシフェラーゼトランスジェニックマウスを用いて、GATA-1とGATA-2の個体レベルでの発現を非侵襲的かつ経時的に解析する系を確立した。G1-HRDルシフェラーゼトランスジェニックマウスにおけるルシフェラーゼ発現を生体用ルミノメーターで解析したところ、その発現はストレス造血において脾臓で著しく増加していた。本系はGATA-1の造血恒常性維持における役割を解析するうえできわめて有効である。

Research Products

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