抗癌剤治療を継続していく上で薬剤耐性獲得が問題となるため, 様々な耐性遺伝子解析法が行われているが, 我々はトランスポゾンを用いたまったく新しい網羅的な薬剤耐性遺伝子のスクリーニングを行った。本手法の利点は, 任意の細胞株と分子標的薬を含む任意の抗癌剤の組み合わせで, 薬剤耐性遺伝子の解析が可能となる点であり, 我々はこの手法を用いて「食道扁平上皮癌・放射線耐性」「Luminal乳癌・エリブリン」「HER2陽性乳癌・ラパチニブ」等, 複数の組み合わせについて候補遺伝子の蓄積を行った。今後は本手法を用いて様々な応用を行い, トランスレーショナルリサーチとして臨床応用を試みていく。
Drug resistance is one of the major issues in managing esophageal cancer patients as chemotherapy is a pillar treatment today. Since drug resistance may be mediated by genetic changes in the tumor, the identification of gene mutation may lead to better outcomes in therapy. We performed a novel method using transposon for a comprehensive screening with a view to identify drug resistant genes. Transposons are DNA sequences that move from one location on the genome to another. By this nature, a modified piggyBac transposon was designed as an insertion mutagen. A cytomegalovirus (CMV) promoter sequence was added to initiate strong transcription. When the transposon is inserted to the upstream of a certain gene, the gene will be up-regulated while when inserted downstream of intragenicaly it will be down regulated. The method is inexpensive and relatively simple, and capable both in activation and disruption, leading to comprehensive screening.

研究種目 : 基盤研究(C)(一般)
研究期間 : 2013～2015
課題番号 : 25461997
研究分野 : 乳腺外科学