摘要
目的探索鼻咽癌(nasopharyngeal carcinoma,NPC)中表皮生长因子受体(epidermal growth factor receptor,EGFR)调控β淀粉样蛋白前体(amyloid beta A4protein,APP)的信号通路及其临床意义。方法采用转化生长因子(transforming growth factors-α,TGF-α)诱导CNE2细胞24h作为研究模型,分别采用EGFR酪氨酸激酶的选择性小分子抑制剂PD153035,MAPK抑制剂PD98059,PI3K抑制剂Wortmannin处理2h再用TGF-α作用24h作为实验组,Western blot检测阻断剂APP蛋白的表达和分泌变化情况。免疫组化检测EGFR和APP蛋白在NPC与慢性鼻咽炎症上皮组织中的表达差异。结果PD153035+TGF-α组APP蛋白表达与分泌有所下调,wortmannin+TGF-α组APP蛋白下调明显,PD98059+TGF-α组APP表达无明显变化。EGFR和APP在NPC组织中的表达高于鼻咽炎症上皮组织,且差异有统计学意义(P<0.05)。结论NPC中APP蛋白主要受EGFR信号通路中的PI3K调控,EGFR和APP与NPC的发生有关。
Objective To explore the signaling pathway involved in the activation of amyloid beta A4 protein（APP） expression regulated by epidermal growth factor receptor（EGFR） in CNE2 cells, and the potential significance of EGFR and APP in the occurrence of NPC. Methods CNE2 cells were stimulated with TGF-α for 24 h as a model for this study. The cells were treated with specific inhibition of EGFR （ PD 153035 ）, the Pt3 K inhibitor （Wortmannin） and the MAPK inhibitor （PD98059） for 2 h, respectively, followed by stimulation with TGF-α for 24 h. And then the expression of APP was determined by Western blot. lmmunohistochemistry was performed to detect the differential expression of EGFR and APP in the tumor tissues and nasopharyngeal inflammation mucous tissues. Results The expression of APP was partly inhibited in PD153035 treated group, drastically down-regulated in wortmannin treated group, while there was no obvious change in PD98059 treated group. EGFR and APP expressed higher in the tumor tissues than in the nasopharyngeal inflammation mucous tissues. Conclusion EGFR can regulate APP expression mainly through the PI3K pathway. EGFR and APP expression are related to NPC occurrence.
出处
《山西医科大学学报》
CAS
2009年第8期706-708,F0003,共4页
Journal of Shanxi Medical University
基金
湖南省科学技术厅计划重点项目资助(06SK2004)
关键词
鼻咽癌
表皮生长因子受体
淀粉样蛋白前体
信号通路
nasopharyngeal carcinoma
epidermal growth factor receptor
amyloid beta A4 protein
signaling pathway
