神经胶质瘤中β-抑制蛋白1的表达及意义

文普帅* 高静 李文慧 席焕久

解剖学报 ›› 2014, Vol. 45 ›› Issue (6) : 779-784.

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解剖学报 ›› 2014, Vol. 45 ›› Issue (6) : 779-784. DOI: 10.3969/j.issn.0529-1356.2014.06.009
神经生物学

神经胶质瘤中β-抑制蛋白1的表达及意义

  • 文普帅1*高静2 李文慧3,席焕久3
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Expression and significance of arrestin beta 1 in patients with glioma

  • WEN Pu-shuai 1*GAO Jing2 LI Wen-hui3 XI Huan-jiu3
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摘要

目的 检测神经胶质瘤中β-抑制蛋白1(ARRB1)的表达水平及临床意义。方法 采用RT-PCR和Western blotting 检测胶质瘤细胞系中ARRB1的表达水平;通过肿瘤微阵列数据库(Oncomine)及Project Betastasis平台分析ARRB1 mRNA在神经胶质瘤中的表达情况;采用免疫组织化学方法检测神经胶质瘤组织及瘤旁脑组织中ARRB1的表达水平;应用Kaplan Meier分析ARRB1的表达水平与胶质瘤患者预后的关系。 结果 与正常人脑组织和人胚肾细胞系(HEK293)相比,神经胶质瘤细胞系中ARRB1的mRNA和蛋白水平降低;Oncomine数据库结果显示,多个神经胶质瘤基因芯片中ARRB1 mRNA水平较正常对照组明显降低(P<0.001),ARRB1在恶性程度较高的胶质母细胞瘤中下降程度更加明显;免疫组织化学结果显示,与瘤旁脑组织相比神经胶质瘤中ARRB1表达降低,而且Ⅲ-Ⅳ期较Ⅰ-Ⅱ期神经胶质瘤降低更加明显。此外,Kaplan-Meier生存曲线结果显示,ARRB1的表达水平与神经胶质瘤患者的生存时间存在相关性(P<0.05)。 结论 神经胶质瘤ARRB1水平下调,可作为反映神经胶质瘤临床病理学特点的指标;另外,ARRB1可作为判断神经胶质瘤患者预后的生物标志物。

Abstract

Objective To detect the expression levels of arrestin beta 1 (ARRB1) in patients with glioma, and assess its clinical significance. Methods The expression levels of ARRB1 in glioma cell lines were detected by RT-PCR and Western blot; ARRB1 mRNA expression in glioma was analyzed from Oncomine database and Project Betastasis platform; the expression of ARRB1 in glioma and peritumoral brain tissue was detected by immunohistochemistry; the association of ARRB1 expression levels with the prognosis of patients was analyzed by Kaplan Meier method. Results Compared with normal brain tissue and cell line HEK293, the mRNA and protein levels of ARRB1 in glioma cell lines were reduced; Oncomine database showed ARRB1 mRNA levels in multiple glioma microarray were significantly lower than the normal control group (P<0.001), specially in highly malignant glioblastoma. Immunohistochemistry data showed that ARRB1 expression in glioma tissues was reduced compared with the peritumoral brain tissue, and the expression of ARRB1 in Ⅲ-Ⅳ stage of gliomas was reduced more significantly than that in stage Ⅰ-Ⅱ glioma. In addition, Kaplan-Meier survival curves showed that the expression level of ARRB1 in glioma was correlated with patients survival (P<0.05). Conclusion Reduced ARRB1 expression level in glioma could be used to evaluate the clinical and pathological features of glioma, and the ARRB1 can be used a biomarker to judge the prognosis of patients with glioma.

关键词

神经胶质瘤 / β-抑制蛋白1 / 预后 / 免疫组织化学 /

Key words

Glioma / Arrestin beta 1 / Prognosis / Immunohistochemistry / Human

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文普帅* 高静 李文慧 席焕久. 神经胶质瘤中β-抑制蛋白1的表达及意义[J]. 解剖学报. 2014, 45(6): 779-784 https://doi.org/10.3969/j.issn.0529-1356.2014.06.009
WEN Pu-shuai*GAO Jing LI Wen-hui XI Huan-jiu. Expression and significance of arrestin beta 1 in patients with glioma[J]. Acta Anatomica Sinica. 2014, 45(6): 779-784 https://doi.org/10.3969/j.issn.0529-1356.2014.06.009

参考文献

[1]Sterne-Marr R, Gurevich VV, Goldsmith P, et al.Polypeptide variants of beta-arrestin and arrestin3[J].J Biol Chem,1993,268(21):15640-15648.
[2]Oakley RH, Laporte SA, Holt JA, et al.Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors[J].J Biol Chem,2000,275(22):17201-17210.
[3]Ferguson SS, Downey WE 3rd, Colapietro AM, et al. Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization [J]. Science, 1996, 271 (5247):363-366.
[4]Bryja V, Schambony A, Cajánek L, et al. Beta-arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways[J].EMBO Rep,2008,9(12):1244-1250.
[5]Chen W, ten Berge D, Brown J, et al. Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4[J]. Science,2003,301(5638):1391-1394.
[6]Chen W, Kirkbride KC, How T,et al. Beta-arrestin 2 mediates endocytosis of type Ⅲ TGF-beta receptor and down-regulation of its signaling[J].Science, 2003,301(5638):1394-1397.
[7]Mukherjee A, Veraksa A, Bauer A, et al. Regulation of Notch signalling by non-visual betaarrestin [J].Nat Cell Biol,2005,7(12):1191-1201.
[8]Barnes WG, Reiter E, Violin JD, et al. Beta-arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation[J].J Biol Chem,2005,280 (9): 8041-8050.
[9]Zoudilova M, Kumar P, Ge L,et al. Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2[J].J Biol Chem,2007,282(28):20634-20646.
[10]Gao H, Sun Y, Wu Y, et al. Identification of beta-arrestin 2 as a G protein-coupled receptor-stimulated regulator of NF-kappa B pathways[J].Mol Cell,2004,14(3):303-317.
[11]Witherow DS, Garrison TR, Miller WE, et al. Beta-arrestin inhibits NF-kappa B activity by means of its interaction with the NF-kappa B inhibitor Ikappa B alpha[J].Proc Natl Acad Sci USA, 2004,101(23):8603-8607.
[12]Li TT, Alemayehu M, Aziziyeh AI, et al. Beta-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells[J]. Mol Cancer Res, 2009,7 (7) :1064-1077.
[13]Michal AM, Peck AR, Tran TH, et al. Differential expression of arrestins is a predictor of breast cancer progression and survival[J].Breast Cancer Res Treat,2011,130(3):791-807.
[14]Dasgupta P, Rastogi S, Pillai S, et al. Nicotine induces cell proliferation by beta-arrestin-mediated activation of Src and Rb-Raf-1 pathways[J].J Clin Invest,2006,116(8): 2208-2217.
[15]Raghuwanshi SK, Nasser MW, Chen X, et al. Depletion of beta-arrestin-2 promotes tumor growth and angiogenesis in a murine model of lung cancer[J].J Immunol, 2008, 180 (8) :5699-5706.
[16]Sun X, Zhang Y, Wang J, et al. Beta-arrestin 2 modulates resveratrol-induced apoptosis and regulation of Akt/GSK3β pathways[J].Biochim Biophys Acta, 2010,1800(9):912-918.
[17]Zhao M, Zhou G, Zhang Y, et al. Beta-arrestin 2 inhibits opioid-induced breast cancer cell death through Akt and Caspase-8 pathways[J].Neoplasma,2009,56(2):108-113.
[18]Rosanò L, Cianfrocca R, Masi S, et al. Beta-arrestin links endothelin a receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis[J].Proc Natl Acad Sci USA,2009, 106(8):2806-2811. 
[19]Kim JI, Lakshmikanthan V, Frilot N, et al. Prostaglandin E2 promotes lung cancer cell migration via EP4-betaArrestin1-c-Src signalsome[J].Mol Cancer Res,2010,8(4):569-577.
[20]Mythreye K, Blobe GC. The type Ⅲ TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42 [J].Proc Natl Acad Sci USA,2009,106(20):8221-8226.
[21]Zou L, Yang R, Chai J,et al. Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis[J].FASEB J,2008,22(2):355-364.
[22]Benovic JL, Kühn H, Weyand I,et al. Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein)[J].Proc Natl Acad Sci U S A,1987,84(24):8879-8882.
[23]Mandell JW, Glass G, Gianchandani EP, et al. Dephosphorylation of beta-arrestin 1 in glioblastomas [J]. J Neuropathol Exp Neurol, 2009, 68(5):535-541.
[24]Jansen M, Yip S, Louis DN. Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers[J].Lancet Neurol, 2010,9(7):717-726.
[25]Rubin JB, Kung AL, Klein RS, et al. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors[J]. Proc Natl Acad Sci USA, 2003,100 (23): 13513-13518.
[26]Gravel S, Malouf C, Boulais PE, et al. The peptidomimetic CXCR4 antagonist TC14012 recruits beta-arrestin to CXCR7: roles of receptor domains[J]. J Biol Chem, 2010, 285(49):37939-37943.
[27]Hartmann C, Hentschel B, Tatagiba M,et al. Molecular markers in low-grade gliomas: predictive or prognostic [J] ?Clin Cancer Res,2011,17(13):4588-4599.


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