ネズミの線維芽細胞にヒトの変形成長因子-αcDNAが発現すると,変形が生じます

A Rosenthal, P B Lindquist, T S Bringman

Cell

|July 18, 1986

まとめ

ラット-1細胞による成長因子アルファ (TGF-alpha) 生産の変容は悪性変容を誘発し,腫瘍形成につながった. 中和抗体は,この腫瘍促進効果を阻害し,TGF-α を確認した.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
腫瘍学腫瘍学

背景:

トランスフォーミング成長因子アルファ (TGF-alpha) などの成長因子は,細胞増殖を促し,悪性変異につながる可能性があります.
腫瘍細胞はしばしばTGF-αを分泌し,がんの発症におけるオトクリン刺激モデルをサポートする.

研究の目的:

細胞腫瘍発生性におけるTGF-αの役割を直接調査する.
TGF-αの発現が不変形細胞における悪性変異を誘発するのに十分であるかどうかを判断する.

主な方法:

ヒトのTGF-αcDNA発現ベクトルを,既定の非変形フィッシャーラット線維芽細胞 (ラット-1) に導入.
ヌードマウスにおけるアンカレーズ依存成長と腫瘍形成の評価.
抗ヒトTGF-αモノクローナル抗体による軟アガールにおけるコロニー形成の抑制.

主要な成果:

人間のTGF-alphaを合成し分泌するように設計されたラット-1細胞は,アンカレージに依存する成長の喪失を示した.
これらのTGF-αを発現するラット-1細胞は,裸のマウスの腫瘍を形成し,誘発性腫瘍発生性を示した.
抗ヒトTGF-alphaモノクローナル抗体は,TGF-alphaを発現する細胞による軟アガールにおけるコロニー形成を効果的に防止した.

結論:

TGF-αのオトクリン生成は,変異していない線維芽細胞における悪性変異と腫瘍発生性を誘発するのに十分である.
TGF-alphaのシグナル伝達を抗体で標的化することで,TGF-alphaの腫瘍促進効果を抑制することができます.

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