人間の乳がん:エストロゲン受容体によって媒介されるアンドロゲン作用

D T Zava, W L McGuire

Science (New York, N.Y.)

|February 17, 1978

まとめ

アンドロゲンは,高用量でのみ乳がん細胞の成長を促進し,アンドロゲン受容体ではなくエストロゲン受容体を通して作用します. この発見は,ホルモン主導の癌の進行に関する理解に影響を与えます.

科学分野:

エンドクリノロジーエンドクリノロジー
分子生物学は分子生物学である.
がん研究がん研究

背景:

アンドロゲンは細胞成長に影響を及ぼすことが知られているが,MCF-7のようなヒト乳がん細胞系におけるその特定の役割は複雑である.
アンドロゲンの生理学的濃度では,アンドロゲン受容体 (AR) をMCF-7細胞の核に転位させるが,重大なミトゲン効果はない.

研究の目的:

アンドロゲンがMCF-7細胞の成長に影響するメカニズムを調査する.
アンドロゲンが,アンドロゲン受容体または他の経路を通じてMCF-7細胞の増殖を刺激するかどうかを決定する.

主な方法:

ヒト乳がん細胞系MCF-7を利用したものです.
アンドロゲンの生理学的および薬理学的濃度の細胞成長および受容体転位に対する影響を比較する.
DNA合成とエストロゲン依存タンパク質合成の評価.

主要な成果:

アンドロゲンの薬理学的濃度 (生理学的濃度ではない) は,MCF-7細胞の増殖を強めた.
高用量のアンドロゲンは,アンドロゲン受容体 (AR) とエストロゲン受容体 (ER) の核転位を引き起こした.
薬理学的アンドロゲンは,DNAとエストロゲン依存タンパク質合成を著しく増加させた.

結論:

アンドロゲンは,主にアンドロゲン受容体を通してMCF-7細胞の成長を刺激しません.
エストロゲン受容体は,MCF-7細胞における薬理学的アンドロゲンのミトジェニック効果を媒介する.
これは,高用量のアンドロゲンがエストロゲン受容体経路と相互作用し,乳がん細胞の増殖を促進する間接的なメカニズムを示唆しています.

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