Inhibiting CCN1 blocks AML cell growth by disrupting the MEK/ERK pathway.
Inhibiting CCN1 blocks AML cell growth by disrupting the MEK/ERK pathway.
复制标题
抑制 CCN1 通过破坏 MEK/ERK 通路来阻止 AML 细胞生长
DOI：
10.1186/s12935-014-0074-z
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发表时间：
2014
影响因子：
5.8
通讯作者：
Si WK
中科院分区：
文献类型：
--
作者：
Niu CC;Zhao C;Yang Z;Zhang XL;Pan J;Zhao C;Si WK
BackgroundCCN 1在各种肿瘤类型中发挥不同的作用，但关于CCN 1在白血病中的作用知之甚少。我们还评估了抗体或siRNA介导的CCN 1抑制对两种AML细胞系生长的影响结果U937和Kasumi-1细胞CCN 1的表达明显高于其他5种白血病细胞系，CCN 1蛋白在AML骨髓标本中的表达高于正常骨髓标本。在U937和Kasumi-1细胞中用抗体阻断CCN 1可抑制增殖，增加凋亡，下调Bcl-xL和c-Myc表达，上调Bax表达，但对生存素没有影响。siRNA介导的CCN 1下调抑制了U937和Kasumi-1细胞的增殖和集落形成，并增加了阿糖胞苷诱导的凋亡。此外，CCN 1 siRNA减少MEK和ERK磷酸化而不影响β-连环蛋白; CCN 1抗体类似地影响MEK和ERK磷酸化。这些磷酸化的变化可以影响AML细胞中Bcl-xL、c-Myc和Bax的表达。ConclusionsThe data suggests CCN 1是AML中的肿瘤促进剂，其通过MEK/ERK途径上调c-Myc和Bcl-xL，下调Bax。
BackgroundCCN1 plays distinct roles in various tumor types, but little is known regarding the role of CCN1 in leukemia.MethodsWe analyzed CCN1 protein expression in leukemia cell lines and in AML bone marrow samples. We also evaluated the effects of antibody- or siRNA-mediated inhibition of CCN1 on the growth of two AML cell lines (U937 and Kasumi-1 cells) and on the MEK/ERK pathway, β-catenin and other related genes.ResultsU937 and Kasumi-1 cells had markedly higher CCN1 expression than the 5 other leukemia cell lines, and CCN1 protein expression was higher in the AML bone marrow samples than in the normal bone marrow samples. Blocking CCN1 with an antibody in U937 and Kasumi-1 cells suppressed proliferation, increased apoptosis, down-regulated Bcl-xL and c-Myc expression, up-regulated Bax expression, and had no effect on Survivin. siRNA-mediated down-regulation of CCN1 inhibited the proliferation and colony formation of U937 and Kasumi-1 cells and increased cytarabine-induced apoptosis. Furthermore, CCN1 siRNA reduced MEK and ERK phosphorylation without affecting β-catenin; the CCN1 antibody similarly affected MEK and ERK phosphorylation. These changes in phosphorylation could influence the expression of Bcl-xL, c-Myc and Bax in AML cells.ConclusionsThe data suggested that CCN1 is a tumor promoter in AML that acts through the MEK/ERK pathway to up-regulate c-Myc and Bcl-xL and to down-regulate Bax.
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影响因子：
11.4
作者：
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影响因子：
20.3
作者：
Kornblau, Steven M.;Womble, Matthew;Andreeff, Michael
通讯作者：
Andreeff, Michael
影响因子：
8
作者：
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通讯作者：
Liebermann, DA
影响因子：
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作者：
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通讯作者：
Lupu, R
影响因子：
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作者：
Nishioka, Chie;Ikezoe, Takayuki;Yokoyama, Akihito
通讯作者：
Yokoyama, Akihito