表皮生长因子对子宫肌瘤细胞MAPK信号通路的活化作用  

Effect of epidermal growth factor on activation of MAPK signaling pathway in uterine leiomyoma cells.

作　　者：石岩蓉[1] 朱颖军[2] 林琬君[2] 李洋[1] 王悦冰[3] 

机构地区：[1]天津医科大学研究生院,天津300070 [2]天津市中心妇产科医院妇科,天津300100 [3]南开大学医学院,天津300071

出　　处：《现代妇产科进展》2013年第11期892-896,共5页Progress in Obstetrics and Gynecology

基　　金：TSC2在子宫肌瘤中表达调控机制的实验研究(No104)

摘　　要：目的:研究表皮生长因子(EGF)对子宫肌细胞(HM-SMCs)和子宫肌瘤细胞(HL-SMCs)中有丝分裂原激活的蛋白激酶(MAPK)信号转导通路的活化作用。方法:收集30例子宫肌瘤患者的子宫肌瘤组织和正常子宫肌组织进行原代细胞培养。采用激光扫描细胞法(LSC法)检测BrdU渗入率;Western blot法检测p44/42 MAPK及其磷酸化水平和p44/42 MAPK特异性底物ELK-1的表达,MAPK特异性抑制剂PD98059和EGFR受体抑制剂AG1478对p44/42 MAPK表达的抑制作用,以及p44/42 MAPK的时间依赖性表达以及细胞周期相关蛋白p27的表达。结果:EGF诱导p-p44/42 MAPK和ELK-1水平显著上调,HM-SMCs中的表达量显著高于HL-SMCs。AG1478和PD98059可抑制EGF对MAPK的诱导作用。HM-SMCs中p44/42 MAPK对EGF的刺激呈持续平稳的激活,伴随着p27的显著上调;HL-SMCs中则呈快速短暂的激活,伴随着p27低水平上调。结论:EGF通过活化MAPK信号通路促进细胞增殖可能是子宫肌瘤发病的一个重要的机制,为肌瘤的非手术治疗提供了可能。Objective：Compare the activation of MAPK signal pathway in uterine （HM-SMCs） and uterine leiomyoma smooth muscle cells （HL-SMCs） treated by epidermal growth factor （EGF） , to find the possible pathogenesis of human uterine leiomyoma and the possibility of non-operafion treatment. Methods ： Collected 24 pairs of human uterine leiomyoma tissues （HL）and their matched myometrial tissues （HM） for primary cell culture. Brdu incorporation rates were detected. The phosphorylation and expression of p44/42 MAPK were analyzed by Western blot. ELK-1 was tested to confirm the activation of MAPK signal pathway. PD98059 was added to deteete the inhibition of MAPK phosphorylation. The time dependence of the activation of MAPK signal pathway in HM-SMCs and HL-SMCs were analyzed. The expression of cell cycle protein p27 was detected. Results ： EGF made higher expression of p44/42 MAPK,but the expression of p-p44/42 MAPK in HL-SMCs was lower than that in HM-SMCs, which was consistent with the tendency of ELK-1. The specific inhibitor PD98059 could inhibit the effect of EGF. In HM-SMCs, EGF caused sustained stimulation of p44/42 MAPK with significant upregulation of p27. EGF induced transient activation and subsequent inhibition of p44/ 42 MAPK with marginal upregulation of p27 in HL-SMCs. Conclusion： EGF could promotes cell proliferation through the activation of MAPK signaling pathway, which may be one important mechanism in the pathogenesis of uterine leiomyoma, providing the possibility of non operation treatment of leiomyoma.

关 键 词：子宫肌瘤 EGF MAPK P27 

分 类 号：R737.33[医药卫生—肿瘤]