EPO/EPOR-JAK2-STAT5信号传导通路在成釉细胞瘤中表达意义的研究  

A Study of Expression and Significance of JAK2,STAT5,EPO and its Receptor in Ameloblastomas

作　　者：尹晓东[1] 徐建凯[2] 吴衍昌[1] 王伟[1] 焦晓辉[1] 

机构地区：[1]哈尔滨医科大学附属口腔医学院口腔颌面外科,黑龙江哈尔滨150001 [2]哈尔滨医科大学生物信息科学与技术学院,黑龙江哈尔滨150086

出　　处：《现代生物医学进展》2013年第6期1009-1014,共6页Progress in Modern Biomedicine

基　　金：黑龙江省青年科学基金项目(QC2009C91;QC2012C010);黑龙江省卫生厅医学科研课题(2006045;2012-798)

摘　　要：目的:促红细胞生成素(EPO)及其受体(EPOR)具有促进细胞分裂、生存、肿瘤血管新生以及肿瘤细胞的侵润和转移等多种生物学功能。EPO/EPOR激活的蛋白酪氨酸激酶-2(JAK2)、信号转导子和转录激活子5(STAT5)这一信号传导通路导致头颈部鳞癌的侵润,但在成釉细胞瘤中的作用尚不明确。本文将探讨EPO/EPOR-JAK2-STAT5信号通路在AB中的表达及意义,进一步探索AB的发病机制。方法:应用免疫组化法检测9例牙胚(TG)、10例牙源性角化囊肿(OKC)和36例成釉细胞瘤(AB)中上述四种蛋白的表达。结果:EPO在TG和OKC两组之间免疫组化表达水平存在显著性差异(P<0.05);EPOR在OKC分别与TG组、AB组间比较,差异具有显著型(P<0.05)。EPOR在AB的无细胞变异亚型分别与棘皮瘤亚型、颗粒细胞亚型之间比较有显著差异(P<0.05)。JAK2在细胞浆、细胞核中的表达,在TG、OKC、AB三组间比较均有显著性差异(P<0.05)(P<0.01);在细胞变异亚型、棘皮瘤亚型、颗粒细胞亚型之间比较有极显著差异或显著差异(P<0.001)(P<0.01)。STAT5在细胞浆、细胞核中的表达,OKC组分别与TG组、AB组比较,均有显著性差异(P<0.05)。结论:EPO/EPOR-JAK2-STAT5信号通路在TG组、OKC组、AB组之间,以及AB的各分型、亚型之间,表达显著差异。研究结果表明,EPO/EPOR在牙源性组织、瘤样病变、AB中通过JAK2-STAT5信号途径发挥作用,EPO/EPOR-JAK2-STAT5通路的异常活化与成釉细胞瘤的发生、发展有关。Objective： Erythropoietin （EPO） interacted with its receptor （EPOR） is a multi-functional growth factor that promotes cell proliferation, migration and survival, tumor angiogenesis, and tumor cell invasion and metastasis. EPO-mediated invasion by head and neck squamous cell carcinoma （HNSCC） cells is through the Janus kinase 2 （JAK2）-signal transducer and activator of transcription 5 （STAT5） signaling pathway. However, the role of EPO and EPOR within ameloblastoma （AB） remains incompletely understood. There-fore, we further investigated the expression and the significance of EPO/EPOR-JAK2-STAT5 signaling pathway in AB. Methods： Im-munostaining was performed using antibodies for EPO, EPOR, JAK2 and STAT5 in 9 tooth germs （TGs）, 10 Odontogenic keratocysts （OKCs） and 36 ABs. Results： EPO expression was significantly different between TGs and OKCs （P〈0.05）; EPOR expression in OKCs was significantly different not only to TGs and ABs （P〈0.05）, but also that in non-cellular variation subtype was different from that in acan-thomatous subtype and granular subtype respectively （P〈0.05）. JAK2 expression was significantly different not only among TGs, OKCs and ABs （P〈0.05） （P〈0.01）, but also among non-cellular variation subtype, acanthomatous subtype and granular subtype （P〈0.001） （P〈0. 01） in cytoplasm and nucleus respectively. STAT5 expression was significantly different between OKCs and TGs, or OKCs and ABs in cytoplasm and nucleus respectively （P〈0.05）. Conclusions： The expression of EPO/EPOR-JAK2-STAT5 signaling pathway were signifi- cantly different between TG, OKC, and AB, and between certain types or subtypes of AB, indicating that genesis and development of AB was correlated with high expression of EPO and its receptor, and abnormal activation of JAK2-STAT5 signaling pathway. In addition, EPO/EPOR could exert their function mediated by JAK2-STAT5 signaling pathway in odontogenic tissue, tumor-like lesion and AB.

关 键 词：成釉细胞瘤 促红细胞生成素 蛋白酪氨酸激酶-2 信号转导子和转录激活子5 

分 类 号：Q593[生物学—生物化学] Q75