c-jun氨基末端激酶与多药耐药蛋白在胃癌组织中的表达及其意义

目的 研究c-jun氨基末端激酶(e-jun N-terminal kinase,JNK)的磷酸化活性形式p-JNK与多药耐药蛋白P糖蛋白(p-glycoprotein,P-gP)、多药耐药相关蛋白1(multidrng resistance associated proteinl,MRP1)和肺耐药相关蛋白(lung resistance protein,LRP)在胃癌组织中的表达及p-JNK在胃癌耐药中的作用.方法 通过免疫组化方法研究168例胃癌和27例正常胃组织的组织芯片中p-JNK和P-gP、MRP1、LRP的表达及其关系.结果 p-JNK和耐药蛋白P-gP、MRP1、LRP在胃癌组织中的阳性表达率分别为45.8%、51.8%、45.8%和55.4%,均明显高于在正常胃组织中的表达.p-JNK与肿瘤大小、浸润深度、脉管浸润、淋巴结转移和远处转移显著相关.p-JNK与P-gP和MRPl表达正相关(P＜0.01).Kaplan-Meier分析显示p-JNK和P-gp、MRP1阳性组的预后较阴性组差(P＜0.01).结论 p-JNK高表达参与胃癌的恶性生物学行为,通过上调耐药蛋白P-gp和MRP1的表达参与胃癌化疗耐药的形成;p-JNK可成为评价胃癌预后和耐药的有价值指标.

Expression and significance of P-JNK and mutlidrug resistance protein in gastric cancer

Objective To investigate the clinicopathogenical significance of phosphorylation type of c-jun N-terminal kinase(p-JNK)and muhidmg resistance protein P-glycopretein(P-gP),multidrug resistance proteinl(MRP1)and lung resistance protein(LRP)in gastric cancer. Methods The expression of p-JNK,P-gP,MRP1 and LRP was detected in a tissue microarray containing 168 spots of gastric cancer tissue and 27 spots of normal gastric tissue by immunohistochemistry.Results The positive expression rate of p-JNK,P-gp,MRP1 and LRP in gastric cancer wag 45.8%,51.8%,45.8%and 55.4%respectively,which Was significantly higher than that in normal gastric tissue(P＜0.05).The p-JNK expression correlated with depth of invasion(P＜0.01),histology grade(P＜0.05),vessel invasion (P＜0.01),lymph node metastasis and distant metastasis(P＜0.01).The expression of p-JNK,P-gp and MRP1 in a positive relationship(P＜0.05).Kaplan-Meier analysis revealed a significant impact on survival by p-JNK,P-gp and MRPl(P＜0.05). Conclusion The p-JNK expression in gastric cancer is correlated with malignant biological behavior and may be involved in the chemotherapeutic resistance by upregulating the expression of P-g and MRP1.