Notch信号通路在血小板衍生生长因子-BB诱导人胰腺癌细胞增殖过程中的作用

doi:10.3969/j.issn.0529-1356.2014.02.017

解剖学报 ›› 2014 ›› Issue (2) : 239-241. DOI: 10.3969/j.issn.0529-1356.2014.02.017

肿瘤生物学

Notch信号通路在血小板衍生生长因子-BB诱导人胰腺癌细胞增殖过程中的作用

马永超范文娟吴华王福清*

作者信息 +

Role of Notch signaling in platelet derived growth factor-BB induced proliferation of human pancreatic adenocarcinoma

MA Yong-chao FAN Wen-juan WU Hua WANG Fu-qing*

Author information +

文章历史 +

摘要

目的探讨Notch信号通路在血小板衍生生长因子（PDGF)-BB诱导人胰腺癌细胞（HPAC）增殖过程中的作用。方法 MTT法检测PDGF-BB及γ-secretase 抑制剂4’，6-二脒基-2-苯基吲哚（DAPT）对HPAC增殖活力的影响；Western blotting检测细胞Notch蛋白表达水平的变化；染色质免疫共沉淀（CHIP）检测Notch下游靶基因转录水平的变化。结果 PDGF-BB显著促进HPAC增殖，提高细胞Notch表达水平，增强Notch靶基因的转录；不同剂量的DAPT及血小板衍生生长因子受体（PDGFR）抑制剂处理细胞，显著反转了PDGF-BB的作用。结论 Notch信号通路在PDGF-BB诱导胰腺癌细胞增殖中起到重要作用。

Abstract

Objective To clarify Notch signaling in platelet derived growth factor-BB(PDGF-BB) induced proliferation of human pancreatic adenocarcinoma (HPAC). Methods After being treated by PDGF-BB and (or) γ-secretase inhibitor DAPT, changes of HPAC cell proliferation were detected by MTT assay; Alterations of Notch level in HPAC cells were measured by Western blotting assay; Variations of capability in cardiolipin synthetic lecithin(CSL) binding to the promoter of target gene hes-1 were identified by chromatin immunoprecipitation (CHIP) assay. Results PDGF-BB facilitates the proliferation of HPAC cells, upregulates Notch level and enhances the capability in CSL binding to the promoter of hes-1. DAPT and PDGFR inhibitor treatment suppresses and invalidates PDGF-BB effection. Conclusion Notch-1 signaling plays an essential role in the modulation of PDGF-BB-induced proliferation of HPAC cells.

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用

马永超范文娟吴华王福清*. Notch信号通路在血小板衍生生长因子-BB诱导人胰腺癌细胞增殖过程中的作用[J]. 解剖学报. 2014(2): 239-241 https://doi.org/10.3969/j.issn.0529-1356.2014.02.017

MA Yong-chao FAN Wen-juan WU Hua WANG Fu-qing*. Role of Notch signaling in platelet derived growth factor-BB induced proliferation of human pancreatic adenocarcinoma[J]. Acta Anatomica Sinica. 2014(2): 239-241 https://doi.org/10.3969/j.issn.0529-1356.2014.02.017

参考文献

［1］Torrisani J, Bournet B, Cordelier P, et al. New molecular targets in pancreatic cancer［J］. Bull Cancer, 2008,95(5):503-512.
［2］Taeger J, Moser C, Hellerbrand C, et al. Targeting FGFR/PDGFR/VEGFR impairs tumor growth, angiogenesis, and metastasis by effects on tumor cells, endothelial cells, and pericytes in pancreatic cancer ［J］. Mol Cancer Ther, 2011,10(11):2157-2167. 
［3］Rahbari NN, Schmidt T, Falk CS, et al. Expression and prognostic value of circulating angiogenic cytokines in pancreatic cancer ［J］. BMC Cancer, 2011,11:286.
［4］Yuzawa S, Kano MR, Einama T, et al. PDGFRβ expression in tumor stroma of pancreatic adenocarcinoma as a reliable prognostic marker ［J］. Med Oncol, 2012, 29(4):2824-2830.
［5］Ilagan MX, Kopan R. SnapShot: notch signaling pathway ［J］. Cell, 2007, 128(6):1246. 
［6］Golde TE, Koo EH, Felsenstein KM, et al. γ-Secretase inhibitors and modulators ［J］. Biochim Biophys Acta, 2013,1828(12):2898-2907.
［7］Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease ［J］. Nat Rev Mol Cell Biol,2002,3(10):753-766.
［8］Capaccione KM, Pine SR. The Notch signaling pathway as a mediator of tumor survival ［J］. Carcinogenesis, 2013,34(7):1420-1430. 
［9］Ma YC, Shi C, Zhang YN, et al.The tyrosine kinase c-Src directly mediates growth factor-induced Notch-1 and Furin interaction and Notch-1 activation in pancreatic cancer cells ［J］. PLoS One， 2012,7(3):e33414.