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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 63 - 68 (6page)
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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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참고문헌 (23)
참고문헌 신청
Powell JD / 2012 / Regulation of immune responses by mTOR / Annu Rev Immunol 30:39~68
Laplante M / 2012 / mTOR signaling in growth control, disease / Cell 149:274~293
Zeng H / 2013 / mTOR, lymphocyte metabolism / Curr Opin Immunol 25:347~355
Lee K / 2010 / Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1, Th2 cell subsets via distinct signaling pathways / Immunity 32:743~753
Lee K / 2013 / Requirement for Rictor in homeostasis, function of mature B lymphoid cells / Blood 122:2369~2379
Laplante M / 2012 / mTOR signaling in growth control, disease / Cell 149:274~293
Zeng H / 2013 / mTOR, lymphocyte metabolism / Curr Opin Immunol 25:347~355
Lee K / 2010 / Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1, Th2 cell subsets via distinct signaling pathways / Immunity 32:743~753
Lee K / 2013 / Requirement for Rictor in homeostasis, function of mature B lymphoid cells / Blood 122:2369~2379
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