연구논문

세부과제번호 2014M3A9D5A01073841 단계 1단계 3차년도
세부과제명 마우스 면역표현형 및 감염 면역반응성 분석 기술 구축과 서비스 기반 확립 공동 유/무 -
SCI여부 Y 게재년월 2016-01
논문제목 Rapamycin-resistant and torin-sensitive mTOR signaling promotes the survival and proliferation of leukemic cells.
총저자명 Seohyun ParkHyunsub SimKeunwook Lee
학술지명 BMB Rep 게재권(호) 49(1)
저널구분 - 페이지수 63-68
참여연구원 이근욱 연구책임자 이근욱
과제기여도 25 PMID 26497580
사사기관수 - IF (년도) 2.595
제1저자 박서현 교신저자 이근욱
공동저자 -
초록
The serine/threonine kinase mTOR is essential for the phosphoinositide 3-kinases (PI3K) signaling pathway, and regulates the development and function of immune cells. Aberrant activation of mTOR signaling pathway is associated with many cancers including leukemia. Here, we report the contributions of mTOR signaling to growth of human leukemic cell lines and mouse T-cell acute leukemia (T-ALL) cells. Torin, an ATP-competitive mTOR inhibitor, was found to have both cytotoxic and cytostatic effects on U-937, THP-1, and RPMI-8226 cells, but not on Jurkat or K-562 cells. All cells were relatively resistant to rapamycin even with suppressed activity of mTOR complex 1. Growth of T-ALL cells induced by Notch1 was profoundly affected by torin partially due to increased expression of Bcl2l11 and Bbc3. Of note, activation of Akt or knockdown of FoxO1 mitigated the effect of mTOR inhibition on T-ALL cells. Our data provide insight on the effect of mTOR inhibitors on the survival and proliferation of leukemic cells, thus further improving our understanding on cell-context-dependent impacts of mTOR signaling.
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