刺猬信号通路激活抑制T淋巴细胞白血病Jurkat细胞的克隆形成并激活NOTCH信号通路。
Hedgehog Stimulation Suppresses Clonogenicity and Activates NOTCH Signalling in T-lymphoblastic Leukaemia Jurkat Cells.
作者信息
Okuhashi Yuki, Itoh Mai, Tohda Shuji
机构信息
Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Medical Technology, Tokyo University of Technology, Tokyo, Japan.
出版信息
Anticancer Res. 2017 Sep;37(9):5005-5009. doi: 10.21873/anticanres.11914.
BACKGROUND/AIM: Hedgehog (HH) and NOTCH pathways are involved in the regulation of cancer stem cells and haematopoietic malignancies. However, the effects of HH stimulation on cell growth and NOTCH signalling in acute T-lymphoblastic leukaemia (T-ALL) cells have not been elucidated.
MATERIALS AND METHODS
Two T-ALL cell lines, Jurkat and KOPT-K1 harbouring activating NOTCH1 mutations, were cultured with recombinant Sonic (S) HH and analysed for proliferation, colony formation, and expression of NOTCH-regulated genes and proteins.
RESULTS
SHH stimulation did not affect cell growth but suppressed colony formation, increased the levels of cleaved NOTCH1 fragment characteristic for NOTCH1 activation, and upregulated mRNA expression of HES1, while decreasing that of MYC in Jurkat cells. However, no such effects were observed in KOPT-K1 cells.
CONCLUSION
Our results indicate that SHH stimulation activates NOTCH signalling in Jurkat cells, thus disclosing a novel relationship between HH and NOTCH pathways.
背景/目的：刺猬信号（HH）和Notch信号通路参与癌症干细胞和血液系统恶性肿瘤的调控。然而，HH刺激对急性T淋巴细胞白血病（T-ALL）细胞的细胞生长和Notch信号的影响尚未阐明。
材料与方法
使用携带激活型Notch1突变的两种T-ALL细胞系Jurkat和KOPT-K1，用重组音猬因子（S）HH进行培养，并分析其增殖、集落形成以及Notch调控基因和蛋白的表达。
结果
SHH刺激不影响细胞生长，但抑制集落形成，增加Notch1激活特征性的切割Notch1片段水平，并上调Jurkat细胞中HES1的mRNA表达，同时降低MYC的表达。然而，在KOPT-K1细胞中未观察到此类效应。
结论
我们的结果表明，SHH刺激激活Jurkat细胞中的Notch信号，从而揭示了HH和Notch信号通路之间的新型关系。
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