Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells.
Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells.
复制标题
βcellulin 对肺癌细胞产生 CXCL8 的调节机制
DOI：
10.1186/1479-5876-12-70
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发表时间：
2014-03-16
影响因子：
7.4
通讯作者：
Chen C
中科院分区：
文献类型：
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作者：
Shi L;Wang L;Wang B;Cretoiu SM;Wang Q;Wang X;Chen C
背景β细胞素（Betacellulin，BTC）是表皮生长因子（epidermal growth factor，EGF）家族的一员，能结合并激活ErbB 1和ErbB 4同源二聚体。BTC在肿瘤中表达，并参与肿瘤的生长进程。CXCL 8（interleukin-8）通过表皮生长因子受体（epidermal growth factor receptor，EGFR）的反式激活参与肿瘤细胞的增殖。材料与方法本研究旨在探讨BTC与CXCL 8在人肺癌细胞（A549）中可能的相互关系，并阐明细胞内信号在这两种功能调节中的机制。结果BTC通过激活EGFR-PI 3 K/Akt-Erk信号通路，显著增加A549细胞CXCL 8的表达。BTC可诱导人肺癌细胞对TNF-α/CHX诱导的凋亡产生抵抗。PI 3 K抑制剂，Erk 1/2抑制剂，或厄洛替尼治疗显着抑制BTC诱导的CXCL 8的生产和细胞增殖和movement.ConclusionOur数据表明，CXCL 8生产从肺癌细胞可以启动自分泌机制或外部来源的BTC通过EGFR-PI 3 K-Akt-Erk通路的炎症微环境的形成。BTC可能作为监测和改善肺癌炎症发展的潜在靶点。
BackgroundBetacellulin (BTC), a member of the epidermal growth factor (EGF) family, binds and activates ErbB1 and ErbB4 homodimers. BTC was expressed in tumors and involved in tumor growth progression. CXCL8 (interleukin-8) was involved in tumor cell proliferation via the transactivation of the epidermal growth factor receptor (EGFR).Materials and methodsThe present study was designed to investigate the possible interrelation between BTC and CXCL8 in human lung cancer cells (A549) and demonstrated the mechanisms of intracellular signals in the regulation of both functions. Bio-behaviors of A549 were assessed using Cell-IQ Alive Image Monitoring System.ResultsWe found that BTC significantly increased the production of CXCL8 through the activation of the EGFR-PI3K/Akt-Erk signal pathway. BTC induced the resistance of human lung cancer cells to TNF-α/CHX-induced apoptosis. Treatments with PI3K inhibitors, Erk1/2 inhibitor, or Erlotinib significantly inhibited BTC-induced CXCL8 production and cell proliferation and movement.ConclusionOur data indicated that CXCL8 production from lung cancer cells could be initiated by an autocrine mechanism or external sources of BTC through the EGFR–PI3K–Akt–Erk pathway to the formation of inflammatory microenvironment. BTC may act as a potential target to monitor and improve the development of lung cancer inflammation.
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DOI：
10.1158/1078-0432.ccr-08-2921
发表时间：
2009-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sun M;Behrens C;Feng L;Ozburn N;Tang X;Yin G;Komaki R;Varella-Garcia M;Hong WK;Aldape KD;Wistuba II
通讯作者：
Wistuba II
影响因子：
10
作者：
Ganesan S;Unger BL;Comstock AT;Angel KA;Mancuso P;Martinez FJ;Sajjan US
通讯作者：
Sajjan US
通过在AECOPD患者中将炎症介体与临床信息学相结合：一项初步研究，选择了疾病特异性的生物标志物。
影响因子：
5.3
作者：
Chen H;Song Z;Qian M;Bai C;Wang X
通讯作者：
Wang X
影响因子：
4.8
作者：
Liu, Kenneth;Gualano, Rosa C.;Bozinovski, Steven
通讯作者：
Bozinovski, Steven
影响因子：
3.3
作者：
Dobashi, Yoh;Suzuki, Shioto;Ooi, Akishi
通讯作者：
Ooi, Akishi