ポリコンブ群タンパク質EZH2は前立腺がんの進行に関与しています

Sooryanarayana Varambally¹, Saravana M Dhanasekaran, Ming Zhou

¹Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

Nature

|October 11, 2002

まとめ

前立腺がんにおけるゼステホモログ2 (EZH2) の増強剤の過剰発現は,転移と悪い予後と相関しています. EZH2を阻害すると,がん細胞の増殖が減り,前立腺がんの治療標的として示唆される.

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:

前立腺がんは男性がんによる死亡の重要な原因であり,転移型は不治である.
局所性前立腺がんには効果的な治療法がありますが,進行段階では大きな臨床的課題があります.

研究の目的:

前立腺がんの進行におけるゼステホモログ2 (EZH2) の強化剤の役割を調査する.
EZH2発現レベルが疾患のステージと患者の予後と相関するかどうかを判断する.

主な方法:

転移性前立腺がんにおける差異的に発現する遺伝子を特定するための遺伝子発現プロファイリング.
小型の干渉RNA (siRNA) を利用して,前立腺がん細胞におけるEZH2発現を抑制する.
EZH2調節が細胞増殖と遺伝子転写に与える影響を評価する.

主要な成果:

ゼステホモログ2 (EZH2) の強化剤は,ホルモン抵抗性,転移性前立腺がんにおいて著しく過剰発現している.
siRNA媒介によるEZH2抑制による前立腺がん細胞増殖のノックダウン in vitro.
エクトピックEZH2発現は,そのSETドメインとヒストン脱酸化酵素活性に依存する特定の遺伝子の転写抑制につながった.

結論:

調節不良のEZH2発現は,前立腺がんの進行と転移に関与しています.
EZH2濃度の上昇は,局所性前立腺がんの予後が悪いことと関連しています.
EZH2は,積極性前立腺がんと怠惰性前立腺がんを区別するための潜在的なバイオマーカーであり,治療標的である.

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