Hypoxia Up-regulates HIF Expression While Suppressing Cell Growth and NOTCH Activity in Leukaemia Cells.
Hypoxia Up-regulates HIF Expression While Suppressing Cell Growth and NOTCH Activity in Leukaemia Cells.
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DOI：
10.21873/anticanres.13575
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发表时间：
2019-08-01
影响因子：
2
通讯作者：
Tohda, Shuji
中科院分区：
文献类型：
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作者：
Itoh, Mai;Okuhashi, Yuki;Tohda, Shuji
目的：研究缺氧对白血病细胞体外生长及信号蛋白活性的影响，以更好地了解人骨髓白血病细胞的病理生理。材料与方法：在常氧或缺氧条件下培养6株人白血病细胞系。观察细胞生长、克隆细胞恢复、各种信号蛋白的表达和激活。结果：缺氧可抑制细胞生长和克隆原细胞的恢复。此外，缺氧可上调缺氧诱导因子（HIF） 1 α和hif2 α的表达，同时抑制NOTCH1、雷帕霉素激酶（mTOR）活化机制靶点和核因子- κ B （nf - κ B）磷酸化的表达和激活。结论：我们发现缺氧可上调HIF的表达，同时抑制白血病细胞的自我更新能力、NOTCH活性及其下游信号分子的表达，这与以往报道的HIF激活NOTCH信号不同。我们的发现有助于进一步阐明白血病细胞的体内病理生理。
AIM: To examine the influence of hypoxia on the in vitro growth of leukaemia cells and the activity of signalling proteins to better understand the pathophysiology of leukaemia cells in human bone marrow.MATERIALS AND METHODS: Six human leukaemia cell lines were cultured under normoxic or hypoxic conditions. Cell growth, recovery of clonogenic cells, and the expression and activation of various signalling proteins were examined.RESULTS: Hypoxia suppressed cell growth and the recovery of clonogenic cells. Moreover, hypoxia up-regulated hypoxia-inducible factor (HIF) 1alpha and HIF2alpha expression while suppressing the expression and activation of NOTCH1, mechanistic target of rapamycin kinase (mTOR) activation, and nuclear factor-kappa B (NF-kappaB) phosphorylation.CONCLUSION: We found that hypoxia up-regulated HIF expression while it suppressed the self-renewal capacity of leukaemia cells, NOTCH activity, and expression of its down-stream signalling molecules, which differs from previous reports mentioning that HIF activates NOTCH signalling. Our findings serve to further elucidate the in vivo pathophysiology of leukaemia cells.