ヒトの甲状腺がんにおけるPAX8-PPARgamma1融合腫瘍遺伝子 [修正]
T G Kroll1, P Sarraf, L Pecciarini
1Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. tkroll@rics.bwh.harvard.edu
Science (New York, N.Y.)
|August 26, 2000
まとめ
新しい遺伝子融合であるPAX8-PPARgamma1が,甲状腺小胞性癌で特定され,がんの発症を誘発している. この発見は,甲状腺がんに対する新たな診断と治療戦略の可能性を秘めています.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 融合オンコタンパク質を生成する染色体転位は,白血病/リンパ腫および肉腫において一般的です.
- これらの転位は,最も一般的なヒトがんである癌では一貫して観察されていません.
- 甲状腺小胞がんの発症を誘発する特定の遺伝的変異については,さらなる解明が必要である.
研究 の 目的:
- ヒトの甲状腺小胞性癌のサブセットの基礎にある分子メカニズムを調査する.
- 甲状腺がんに関連する新しい遺伝子融合を特定し,特徴づけること.
- 腫瘍発生における同定された融合タンパク質の機能的役割を調査する.
主な方法:
- 染色体転位を特定するためのカリオタイプ分析.
- 融合トランスクリプトを検出するための逆転写-ポリメラーゼ連鎖反応 (RT-PCR).
- 融合産物のタンパク質発現を確認するためのウェスタン・ブロッティング.
- 融合タンパク質が遺伝子トランザクティベーションに与える影響を評価するための機能検査.
主要な成果:
- 特定の転位,t(2;3)(q13;p25) は,甲状腺の卵泡癌で特定されました.
- この転位により,PAX8-PPARgamma1融合遺伝子が形成されます.
- PAX8-PPARgamma1 mRNAとタンパク質は,研究された8つの甲状腺小胞性癌のうち5つで検出されました.
- 融合タンパク質は,良性甲状腺腫瘍と正常な甲状腺組織では存在しなかった.
- PAX8-PPARgamma1は,ペロキシソーム増殖器活性化受容体ガンマ1 (PPARgamma1) の活性に対する支配的負の抑制を示した.
結論:
- PAX8-PPARgamma1融合腫瘍遺伝子は,甲状腺小胞がんの発生に役割を果たしています.
- ペロキシソーム増殖器活性化受容体ガンマ (PPARgamma) は,この文脈で腫瘍学的機能を持つ可能性があります.
- PAX8-PPARgamma1融合タンパク質は,甲状腺がんの診断のための潜在的なバイオマーカーを表しています.
- PAX8-PPARgamma1融合をターゲットにすることで,甲状腺がん治療の新たな治療戦略を提供することができる.
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Such genes that act...
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