肺耐药相关蛋白基因及基因产物在膀胱移行细胞癌中的表达  

Expression of lung resistance-related protein gene in transitional cell carcinoma of the bladder

作　　者：孔垂泽[1] 朱育焱[1] 马智勇[1] 柳东辉 曾宇[1] 李泽良[1] 

机构地区：[1]中国医科大学附属第一医院泌尿外科,沈阳110001 [2]辽宁省金秋医院泌尿外科

出　　处：《中华外科杂志》2005年第2期118-121,共4页Chinese Journal of Surgery

基　　金：卫生部科学研究基金资助项目(981189)

摘　　要：目的探讨肺耐药相关蛋白(LRP)在膀胱癌组织中的表达及与临床病理参数的关系。方法用半定量逆转录聚合酶链反应(RTPCR)技术,检测66例(Ta期12例,T1期26例,T2期11例,T3期10例,T4期7例;G135例,G219例,G312例)术前未经任何治疗的原发膀胱癌患者癌组织及正常组织中LRP、多药耐药基因1(MDR1)和多药耐药相关蛋白1(MRP1)mRNA表达,并用免疫组化法检测LRP、P53和P63蛋白的表达情况。结果(1)膀胱癌标本中,,LRPmRNA的表达率最高(64%,42/66);(2)LRPmRNA水平,正常膀胱组织(142±036)高于膀胱癌组织(080±033,t=282,P<001);低分级膀胱癌组织(G1为139±042)高于高分级癌组织(G2、G3为072±031,t=414,P<001),浅表膀胱癌组织(136±039)高于浸润癌组织(068±030,t=358,P<005);(3)LRPmRNA表达与MDR1或MRP1表达无关,但与其自身的蛋白表达密切相关(r=089,P<001);(4)LRP蛋白表达与低分级、低分期相关(r=081,P<001;r=078,P<005),但与P53、P63表达无关(P>005)。结论膀胱癌组织中,LRPmRNA与蛋白表达一致,且与肿瘤进展有关,可能是膀胱癌内源性多药耐药的预测指标。Objective To investigate the role of lung resistance-related protein (LRP) in intrinsic multidrug resistance (MDR) of bladder cancer and detect the relationship of LRP expression with the clinical pathologic parameters. Methods 66 patients were studied with newly diagnosed primary bladder cancer(T_a=12,T_1=26,T_2=11,T_3=10,T_4=7;G_1=35,G_2=19,G_3=12). No patient was treated preoperatively with either radiation or chemotherapy. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for measure of mRNA expression for LRP, multidrug-resistance gene1(MDR1), and multidrug resist nce-associated protein1 (MRP1) . Expressions of LRP, P53 and P63 proteins were examined by immunohistochemistry staining. Results LRP mRNA had the highest expression rate (64%,42/66) among three MDR markers in primary bladder cancers without chemotherapy andits level was significantly higher in normal bladder tissue than in TCC of bladder (t=2.82, P<0.01), in low grade than in high grade cancers(t=4.14, P<0.01), and in superficial than in invasive cancers (t=3.58,P<0.05). LRP mRNA expression showed no correlation with either MDR1 or MRP1, but close correlation with LRP protein level (r=0.89,P<0.01). LRP was associated with low-grade (r=0.81,P<0.01) and low-stage (r=0.78,P<0.05) cancers, but not with tumor suppressor P53 or P63 (P>0.05).Conclusions^The grade and stage-related expression pattern of LRP indicates that it may be a predictive index for intrinsic MDR in bladder cancer. Anti-cancer drugs out of the MDR spectrum of LRP may be more effective for patients with early bladder cancer.

关 键 词：LRP 膀胱癌组织 蛋白表达 肺耐药相关蛋白 MRP1 mRNA表达 膀胱移行细胞癌 mRNA水平 膀胱组织 基因产物 

分 类 号：R737.14[医药卫生—肿瘤] R735[医药卫生—临床医学]