日米における乳癌、子宮内膜癌のホルモン環境の検討

• 研究課題/領域番号: 12218201
• 研究種目: 特定領域研究(C)
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 東北大学
• 研究代表者: 笹野 公伸 東北大学, 大学院・医学系研究科, 教授 (50187142)
• 研究分担者: 原田 信広 藤田保健衛生大学, 医学部, 教授 (00189705) ; 鈴木 貴 東北大学, 大学院・医学系研究科, 助手 (10261629)
• 研究期間 (年度): 2000
• 研究課題ステータス: 完了 (2000年度)
• 配分額: 1,200千円 (直接経費: 1,200千円); 2000年度: 1,200千円 (直接経費: 1,200千円)
• キーワード: 子宮内膜癌 / エストロゲン / 17水酸化ステロイド脱水素酵素 / レチノイド / ホルモン環境

研究概要

日本人46例、米国ジョンスホプキンス大学医学部のMark Sher man博士から提供された米国人30例の類内膜内膜腺癌において17β-HSD1,2型を免疫組織化学的に検討した。 日本人症例では更にthin layer chromatography(TLC)を用いて活性を、RT-PCRを用いて酵素のmRNA発現を検討した。 日本人46例では17例(37%)、米国人30例では12例(40%)で癌細胞において17β-HSD2型の発現が認められ、17β-HSD1型は日本人米国人双方でその発現は認められなかった。 日本人症例で行ったRT-PCR,TLCを用いた行った活性の検討も免疫組織化学の結果と良く一致した。 次に我々はこの17β-HSD2型の発現を制御している最も重要な因子の一つと考えられているレチノイドの受容体であるretinoic acid receptor(RAR)α,β and γ及びretinoid X receptor(RXR)α,β and γの発現をこれらの類内膜型子宮内膜癌で検討して17β-HSD2型の発現動態と相関させた。日米双方の症例ともにこれらのレチノイド受容体の内で癌細胞におけるRXRγの発現がもっとも癌細胞における17β-HSD2型の発現動態と相関している事が判明した。生物学的に活性の高いエストロゲンと低いエストロゲンを相互転換させる17β-HSDのうちエストラジオールをエストロンの方に転換させる2型が日米双方の類内膜型子宮内膜癌では腫瘍局所でのホルモン環境の形成の上で非常に重要な作用を果たしていることが考えられた。 叉今回の検討から日米双方の症例ともにRXRγを介したレチノイドの作用が子宮内膜癌の局所での17β-HSD2型の発現の制御に極めて重要な働きをしていることが示唆された。このように類内膜型子宮内膜癌のホルモン環境の日米間の差異の検討において、17β-HSD2型及びその制御機構に関しては共通することが示唆された。

研究成果

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