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.

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