NRG1α和NRG1β在人肾母细胞瘤中表达的差异研究

中国医药导刊 ›› 2020, Vol. 22 ›› Issue (11): 790-793.

NRG1α和NRG1β在人肾母细胞瘤中表达的差异研究

林佳哲1a，1b，林暖1c，赵炜疆1b，2*

1. 汕头大学医学院第一附属医院神经外科a，神经科学中心b，妇产科c，广东汕头 515041；
2. 江南大学无锡医学院细胞生物学教研室，江苏无锡 214122

收稿日期:2020-09-11 修回日期:2020-09-25 出版日期:2020-11-28 发布日期:2020-11-28
基金资助:
国家自然科学基金面上项目[项目编号：81471279；项目名称：硫酸软骨素蛋白聚糖（CSPGs）结合肽联合激动型L1抗体治疗脊髓损伤实验研究]；江南大学人才引进启动经费（项目编号：1285081903200020）；江南大学无锡医学院人才引进启动经费（项目编号：1286010242190060）

Comparison of Expression of NRG1α and NRG1β in Human Nephroblastoma

1. Neurosurgical Departmenta， Center for Neuroscienceb， Obstetrics & Gynecology Departmentc，
The First Affiliated Hospital of Shantou University Medical College， Guangdong Shantou 515041，China；
2. Cell Biology Department， Wuxi School of Medicine， Jiangnan University， Jiangsu Wuxi 214122， China

Received:2020-09-11 Revised:2020-09-25 Online:2020-11-28 Published:2020-11-28

摘要/Abstract

摘要： 目的：探究肾母细胞瘤（Wilms氏瘤，WT）中，类表皮生长因子（EGF）家族成员神经调节蛋白-1（NRG1）的表达和分布情况。方法：采用免疫荧光染色法检测来自20位不同肿瘤级别患者WT组织中NRG1α和NRG1β两个亚型的表达，以0~4分为基础进行免疫染色强度评估。结果： NRG1α与NRG1β均表达于WT肿瘤组织中，且NRG1α表达水平(3.5±0.61)高于NRG1β(2.85±0.59)(P<0.05)。结论： NRG1两种亚型在WT发生发展中均可能发挥作用。NRG1α在WT早期检测上更具应用前景，而定位于细胞膜上的NRG1β可能更能特异地提示肿瘤恶性程度。

关键词: font-size:medium, ">肾母细胞瘤；神经调节蛋白-1；组织芯片；免疫荧光

Abstract: Objective： To investigate the expression and distribution of the two variants (α and β) of neuregulin-1 (NRG1)， an epidermal growth factor (EGF) family member， in different stages of Wilms′ tumor (WT). Methods： Immunofluorescence staining was used to detect the expression of NRG1α and NRG1β in cell nucleus， cytoplasma and cell membrane among 20 human WT tissues with different stages. The intensity of immunostaining was evaluated on 0 to 4 point standard. Results： Both subtypes of NRG1 were expressed in WT， with NRG1α(3.5±0.61) more highly expressed and widely distributed than NRG1β (2.85±0.59) (P<0.05). Conclusion： Both variants of NRG1 play important roles in the development of WT. NRG1α may serve as a potential promising biomarker in the early detection of WT， while NRG1β located on the cell membrane may more specifically indicate tumor malignancy.

Key words: font-size:medium, ">Wilms′ tumor； Neuregulin-1； Tissue chip； Immunofluorescence

中图分类号:

林佳哲a, b, 林暖c, 赵炜疆b, . NRG1α和NRG1β在人肾母细胞瘤中表达的差异研究[J]. 中国医药导刊, 2020, 22(11): 790-793.

LIN Jiazhea, b, LIN Nuanc, ZHAO Weijiangb, . Comparison of Expression of NRG1α and NRG1β in Human Nephroblastoma[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2020, 22(11): 790-793.

参考文献

[1]Nakamura L， Ritchey M. Current management of wilms′ tumor [J]. Curr Urol Rep， 2010， 11(1)：58-65.
     [2]Pritchard-Jones K， Bergeron C， DE Camargo B， et al. Omission of doxorubicin from the treatment of stage Ⅱ-Ⅲ， intermediate-risk Wilms′ tumour (SIOP WT 2001)：an open-label， non-inferiority， randomised controlled trial [J]. Lancet， 2015， 386(9999)：1156-1164.
     [3]Irtan S， Ehrlich PF， Pritchard JK. Wilms tumor： "State-of-the-art" update， 2016 [J]. Semin Pediatr Surg， 2016， 25(5)：250-256.
     [4]Breuleux M. Role of heregulin in human cancer [J]. Cell Mol Life Sci， 2007， 64(18)：2358-2377.
     [5]Falls DL. Neuregulins： functions， forms， and signaling strategies [J]. Exp Cell Res， 2003， 284(1)：14-30.
     [6]Lichtenthaler SF， Lemberg MK， Fluhrer R. Proteolytic ectodomain shedding of membrane proteins in mammals-hardware， concepts， and recent developments [J]. Embo J， 2018， 37(15).
     [7]Holmes WE， Sliwkowski MX， Akita RW， et al. Identification of heregulin， a specific activator of p185erbB2 [J]. Science， 1992， 256(5060)：1205-1210.
     [8]Anna G， Francisco D S， Camps M， et al. Neuregulin， an effector on mitochondria metabolism that preserves insulin sensitivity [J]. Front Physiol， 2020，（11）， DOI：10.3389/fphys.2020.00696.
     [9]Britsch S. The neuregulin-I/ErbB signaling system in development and disease [J]. Adv Anat Embryol Cell Biol， 2007， 19：1-65.
     [10]Stove C， Bracke M. Roles for neuregulins in human cancer [J]. Clin Exp Metastasis， 2004， 21(8)：665-684.
     [11]Montero JC， Rodr Guez-Barrueco R， Oca AA， et al. Neuregulins and cancer [J]. Clin Cancer Res， 2008， 14(11)：3237-3241.
     [12]Li Z， Zhang Y， Zhang Z， et al. A four-gene signature predicts the efficacy of paclitaxel-based neoadjuvant therapy in human epidermal growth factor receptor 2-negative breast cancer [J]. J Cell Biochem， 2019， 120(4)：6046-6056.
     [13]Seoane S， Montero JC， Oca AA， et al. Breast cancer dissemination promoted by a neuregulin-collagenase 3 signalling node [J]. Oncogene， 2016， 35(21)：2756-2765.
     [14]Dunn M， Sinha P， Campbell R， et al. Co-expression of neuregulins 1， 2， 3 and 4 in human breast cancer [J]. J Pathol， 2004， 203(2)：672-680.
     [15]Park BH， Lee SB， Stolz DB， et al. Synergistic interactions between heregulin and peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist in breast cancer cells [J]. J Biol Chem， 2011， 286(22)：20087-20099.
     [16]DE Alava E， Oca AA， Abad M， et al. Neuregulin expression modulates clinical response to trastuzumab in patients with metastatic breast cancer [J]. J Clin Oncol， 2007， 25(19)：2656-2663.
     [17]Gilmour LM， Macleod KG， Mccaig A， et al. Neuregulin expression， function， and signaling in human ovarian cancer cells [J]. Clin Cancer Res， 2002， 8(12)：3933-3942.
     [18]Fluge O， Akslen LA， Haugen DR， et al. Expression of heregulins and associations with the ErbB family of tyrosine kinase receptors in papillary thyroid carcinomas [J]. Int J Cancer， 2000， 87(6)：763-770.
     [19]Williams EE， Trout LJ， Gallo RM， et al. A constitutively active ErbB4 mutant inhibits drug-resistant colony formation by the DU-145 and PC-3 human prostate tumor cell lines [J]. Cancer Lett， 2003， 192(1)：67-74.
     [20]Zhang Z， Karthaus WR， Lee YS， et al. Tumor microenvironment-derived NRG1 promotes antiandrogen resistance in prostate cancer [J]. Cancer Cell， 2020， 38(2)：279-296.
     [21]Venkateswarlu S， Dawson DM， St Clair P， et al. Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells [J]. Oncogene， 2002， 21(1)：78-86.
     [22]Ghanem MA， Van Der Kwast TH， Den Hollander JC， et al. Expression and prognostic value of epidermal growth factor receptor， transforming growth factor-alpha， and c-erb B-2 in nephroblastoma [J]. Cancer， 2001， 92(12)：3120-3129.
     [23]Lin WW， Ou GY， Lin JZ， et al. Neuregulin 1 enhances cell adhesion molecule L1 like expression levels and promotes malignancy in human glioma [J]. Oncol Lett， 2020， 20(1)：326-336.
     [24]Forster JA， Paul AB， Harnden P， et al. Expression of NRG1 and its receptors in human bladder cancer [J]. British Journal of Cancer， 2011， 104(7)：1135-1143.
     [25]Zhao WJ， Schachner M. Neuregulin 1 enhances cell adhesion molecule l1 expression in human glioma cells and promotes their migration as a function of malignancy [J]. J Neuropathol Exp Neurol， 2013， 72(3)：244-255.
     [26]Jones JT， Akita RW， Sliwkowski MX. Binding specificities and affinities of egf domains for ErbB receptors [J]. FEBS Lett， 1999， 447(2-3)：227-231.
     [27]Ross JS， Fakih M， Ali SM， et al. Targeting HER2 in colorectal cancer： The landscape of amplification and short variant mutations in ERBB2 and ERBB3 [J]. Cancer， 2018， 124(7)：1358-1373.
     [28]Forster JA， Paul AB， Harnden P， et al. Expression of NRG1 and its receptors in human bladder cancer [J]. Br J Cancer， 2011， 104(7)：1135-1143.

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