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首页> 外文期刊>Journal of Cellular Physiology >KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of merkel cell carcinoma in vitro.
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KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of merkel cell carcinoma in vitro.

机译：KIT受体激活通过自分泌和旁分泌默克尔细胞干细胞因子刺激增长癌体外。

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摘要

The co-expression of KIT receptor and its ligand stem cell factor (SCF) has been reported in biopsy specimens of Merkel cell carcinoma (MCC). However, the functional role of SCF/KIT in the pathogenesis of this aggressive tumor has not been elucidated. The present study reports expression and effects of SCF and KIT in the Merkel cell carcinoma cell line MCC-1 in vitro. SCF and KIT were endogenously co-expressed in MCC-1 cells. Exogenous soluble SCF modulated KIT receptor mRNA and protein expression, stimulated growth of MCC-1 cells, upregulated endogenous activation of KIT, AKT, and of extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. On the contrary, an inhibitory antibody that neutralized the KIT ligand binding site, reduced growth of MCC-1 cells, as did high doses of the KIT kinase inhibitors imatinib and nilotinib. Also, inhibitors of KIT downstream effectors, U0126 that blocks MEK1/2 as well as wortmannin and LY294002 that inhibit phosphatidylinositol 3-kinase-dependent AKT phosphorylation, inhibited the proliferation of MCC-1 cells. These data support the hypothesis that KIT is activatable by paracrine or autocrine tumor cell-derived SCF and stimulates growth of Merkel cell carcinoma in vitro. Blockade of KIT and the downstream signaling cascade at various levels results in inhibition of Merkel cell carcinoma growth in vitro, suggesting targets for therapy of this cancer.
机译：的co-expression KIT受体及其配体干细胞因子(SCF)已经被报道活检标本的默克尔细胞癌(MCC)。然而,自洽场/工具包的功能作用这种侵略性的肿瘤的发病机理被阐明。表达和自洽场和设备的影响默克尔细胞癌细胞系MCC-1体外。自洽场和工具从内部发生MCC-1细胞。受体信使rna和蛋白质表达,刺激增长MCC-1细胞,调节内源性AKT激活工具包,细胞外signal-regulated激酶(ERK) 1/2信号途径。中和装备配体结合位点,减少MCC-1细胞的增长,高剂量工具包的激酶抑制剂伊马替尼nilotinib。效应器,U0126 MEK1/2以及块渥曼青霉素和LY294002抑制磷脂酰肌醇3-kinase-dependent AKT磷酸化,抑制扩散MCC-1细胞。工具包是激活做通过旁分泌或自分泌肿瘤细胞衍生自洽场和刺激增长默克尔细胞癌体外。并在不同的下游信号级联水平导致默克尔细胞的抑制癌体外生长,表明目标治疗癌症。

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