Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma
Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma
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DOI：
10.1016/j.lungcan.2014.05.001
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发表时间：
2014-08-01
期刊：
影响因子：
5.3
通讯作者：
Ito, Takaaki
中科院分区：
文献类型：
--
作者：
Wael, Hassan;Yoshida, Ryoji;Ito, Takaaki
目的：Notch信号在人类肺癌中的作用仍不清楚，关于Notch配体和受体在肺癌发生发展中的作用，一直存在并仍在争论。本研究旨在探讨Notch1信号在人肺癌细胞增殖和分化中的作用。方法：利用小干扰RNA(SiRNA)技术下调小细胞肺癌(SCLC)、H69AR和SBC-3以及非小细胞肺癌(NSCLC)、A549腺癌(ADC)和H2 170鳞状细胞癌(SCC)中Notch1的表达。此外，我们还将Venus Notch1胞内区(v.NICD)载体导入人小细胞肺癌细胞系H69和H1688。此外，将Notch1激活的H1688细胞注射到免疫低下的Rag2(-/-)JAK3(-/-)小鼠体内，分析肿瘤的体外生长和分化表型。结果：NOTCH1对小细胞肺癌和A549细胞的增殖和凋亡都有抑制作用，但对H2 170细胞株没有影响。Notch1在小细胞肺癌中的过表达显著抑制了细胞的增殖。结论：NOTCH1表达上调抑制了小细胞肺癌细胞的生长和NE的分化，诱导了组织标本中上皮样细胞形态的形成。在非小细胞肺癌中，Notch1的表达对ADC细胞有肿瘤抑制作用，但对SCC细胞无抑制作用。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Objectives: The role of Notch signaling in human lung cancer still remains unclear, and there has been and stills a debate, on the extent to which Notch ligands and receptors are involved in lung cancer development. This study was carried out to investigate the role of Notch1 signaling in the proliferation and differentiation of human lung cancer cells.Methods: We used small interfering RNA (siRNA) technology to down-regulate the expression of Notch1 in small cell lung carcinoma (SCLC) cells; H69AR and SBC-3, as well as in non-small cell lung carcinoma (NSCLC) cells; A549 adenocarcinoma (ADC) and H2170 squamous cell carcinoma (SCC). Also, we transfected venus Notch1 intracellular domain (v.NICD) plasmid into the human SCLC line H69 and H1688. In addition, H1688 cells with activated Notch1 were injected into immune-compromised Rag2(-/-) Jak3(-/-) mice for analysis of ex vivo tumor growth and differentiation phenotype.Results: Notch1 controls cell proliferation and apoptosis in both SCLC and A549; but not in H2170 cell line. Overexpression of Notch1 in SCLC markedly decreased cell proliferation via apoptosis. The subcutaneous tumors arising from xenotransplaned SCLC cells transfected with Notch1 showed "epithelial-like glandular" arrangement, with positive Alcian blue staining and reduction in neuroendocrine markers.Conclusion: Notch1 up regulation has an inhibitory effect on cell growth and NE differentiation in SCLC, with induction of an epithelial-like morphology of cells in tissue samples. In NSCLC, Notch1 expression has a tumor inhibitory effect on ADC cells, but not SCC cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.