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KAKEN_16K10474seika.pdf
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Download
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:211.8 KB
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:Oct 31, 2019 |
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Total downloads since Oct 31, 2019 : 876
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乳癌転移巣ER遺伝子変異とCDK4/6阻害剤の相関検討と効果予測法の確立
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ニュウガン テンイソウ ER イデンシ ヘンイ ト CDK4/6 ソガイザイ ノ ソウカン ケントウ ト コウカ ヨソクホウ ノ カクリツ
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Nyūgan ten'isō ER idenshi hen'i to CDK4/6 sogaizai no sōkan kentō to kōka yosokuhō no kakuritsu
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Correlation of ER gene mutation in breast cancer metastasis with effect of CDK4/6 inhibitor
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高橋, 麻衣子
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タカハシ, マイコ
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Takahashi, Maiko
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慶應義塾大学・医学部 (信濃町)・助教
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Research team head
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科研費研究者番号 : 50348661
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林田, 哲
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ハヤシダ, テツ
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Hayashida, Tetsu
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慶應義塾大学・医学部・講師
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Research team member
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科研費研究者番号 : 80327543
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関, 朋子
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セキ, トモコ
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Seki, Tomoko
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慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 70528900
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2019
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科学研究費補助金研究成果報告書
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2018
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ER陽性進行再発乳癌では、32％においてESR1遺伝子変異が認められ、内分泌治療耐性のメカニズムの一つであると考えられている。本研究では再発転移巣生検検体22例中16例 (64％) に変異を認め、そのうち7例でアロマターゼ阻害薬の投与が行われていた。さらにexon8の変異のうち、Leu536Arg, Tyr537Ser, Asp538Glyの３種類のESR1変異遺伝子をMCF7に導入して変異株の作成を行い、機能解析を行った。その結果ESR1変異細胞株ではTAMの効果はほとんどなく、FUL＋PALの組み合わせにおいて最も効率的にRB-E2F1の経路が遮断され、細胞周期の停止が行われていた。
In ER-positive advanced breast cancer, ESR1 gene mutation is found in 32%, which is considered to be one of the mechanisms for endocrine treatment resistance. In this study, mutations were found in 16 of 22 (64%) relapsed metastatic biopsy specimens, of which 7 were treated with aromatase inhibitors. Furthermore, among the mutations of exon 8, three ESR1 mutant genes of Leu536Arg, Tyr537Ser, and Asp538Gly were introduced into MCF7 to prepare mutant clones, and functional analysis was performed. As a result, in the ESR1 mutant cell line, TAM had little effect, and in the combination of FUL + PAL, the RB-E2F1 pathway was most efficiently blocked and cell cycle arrest was observed.
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研究種目 : 基盤研究(C)(一般)
研究期間 : 2016～2018
課題番号 : 16K10474
研究分野 : 乳腺外科
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| Oct 31, 2019 | | インデックス を変更 |
| Oct 31, 2019 | | 著者 名前,著者 カナ,著者 ローマ字,著者 所属,著者 所属(翻訳),著者 役割,著者 外部リンク,抄録 内容,注記 を変更 |
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