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Spheroid Assay to Measure TGF-β-induced Invasion
Published on: November 16, 2011
ガンにおけるTGFBR1*6Aの体内獲得とシグナル伝達
Boris Pasche1, Thomas J Knobloch, Yansong Bian
1Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine, The Feinberg School of Medicine, Northwestern, University, Chicago, Ill 60611, USA. b-pasche@northwestern.edu
JAMA
|October 6, 2005
まとめ
一般的なTGFBR1*6Aポリモルフィズムは結腸直腸がんの転移によって獲得され,TGF-βシグナル伝達を変化させることで腫瘍の成長を促進する可能性がある. これは,TGFBR1*6Aががんの発症における治療標的であることを示唆している.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 癌の遺伝学 癌の遺伝学
背景:
- I型成長因子ベータ受容体 (TGFBR1) ポリモルフィズムであるTGFBR1*6Aは,がん感受性に関連しています.
- TGFBR1*6Aががんの発症に寄与する正確なメカニズムは,依然としてほとんど解明されていない.
研究 の 目的:
- 主要腫瘍および転移におけるTGFBR1*6Aの体内獲得を調査する.
- TGFBR1*6Aにおける特徴的な3アミノ酸欠失が成熟した受容体または信号配列の一部であるかどうかを判断する.
- ガン細胞におけるTGFBR1*6Aシグナル伝達の機能的影響を調査する.
主な方法:
- 531人のがん患者 (頭頸部,大腸直腸,乳がん) の腫瘍および生殖系組織を分析した.
- 腫瘍細胞系 (MCF-7,DLD-1,SW48) のTGFBR1*6A変異体によるインビトロ転写アッセイと安定した転移.
- TGF-β依存細胞増殖とTGFBR1*6Aの体内獲得の評価.
主要な成果:
- TGFBR1*6Aは,結腸直腸がんの転移の29.5%で,小児腫瘍のより少ない割合で体内的に獲得されました.
- TGFBR1*6Aの体内獲得は,遺伝的不安定性マーカーと関連していなかった.
- 成熟したTGFBR1とTGFBR1*6A受容体は同一で,同じ部位で信号配列が割れた.
- TGFBR1*6Aは,TGF-βの阻害信号を癌細胞の成長刺激信号に変換するように見えた.
結論:
- TGFBR1*6Aは,大腸がんの転移の有意な割合で体内的に獲得され,潜在的な成長の利点を授与します.
- がんにおけるTGFBR1*6Aの機能的効果は,成熟した受容体ではなく,その信号配列によって媒介されるように見える.
- TGFBR1*6Aは,がんにおけるTGF-βシグナル伝達の新しい側面であり,潜在的な治療標的である.
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