化疗后残存乳腺癌组织乳腺癌耐药蛋白和P-糖蛋白的表达及其与上皮间质转化的相关性  

Expression of ABCG2 and p-glycoprotein in residual breast cancer tissue after chemotherapy and their correlation with epitheliai-mesenchymal transition

作　　者：屈洪波[1] 方力[1] 段丽丽[2] 龙孝斌[3] 

机构地区：[1]湖南省郴州市第一人民医院乳腺甲状腺血管外科一,423000 [2]南华大学转化医学研究中心 [3]湖南省郴州市第一人民医院肿瘤外科

出　　处：《中华病理学杂志》2014年第4期236-240,共5页Chinese Journal of Pathology

摘　　要：目的探讨化疗后残存乳腺癌组织乳腺癌耐药蛋白（BCRP／ABCG2）、P-糖蛋白表达及其与上皮问质转化（EMT）的相关性。方法收集乳腺癌标本76例，免疫组织化学EnVision法检测化疗后残存乳腺癌组织ABCG2、P-糖蛋白的表达及EMT相关标志物E—cadherin及波形蛋白的表达。将乳腺癌MCF7细胞分为空白对照组、阳性对照（TGF—B1诱导）组和联合用药组，联合应用多西紫杉醇和表柔比星处理MCF7细胞获得药物筛选残存细胞（DSC）；免疫荧光检测DSC细胞中E—cadherin和波形蛋白的表达；逆转录-聚合酶链反应（RT—PCR）和Westernblot分别检测DSC细胞中ABCG2、P-糖蛋白、E．cadherin、波形蛋白的mRNA及其蛋白表达。结果与化疗前乳腺癌组织比较，化疗后残存乳腺癌组织中高表达ABCG2和P-糖蛋白，并与波形蛋白表达呈显著正相关（r．=0．97，P．=0．000；r2=0．83，P：：0．001）；而与E—cadherin蛋白表达呈显著负相关（r3=-0．55，P，=0．010；r4=-0．43，P4=0．020）。免疫荧光结果亦显示DSC中高表达波形蛋白，而低表达E—cadherin蛋白。RT—PCR显示DSC中高表达ABCG2及P一糖蛋白mRNA，且与波形蛋白的mRNA表达呈显著正相关（r，=0．99，／．2=0．96，P〈0．05）；与E—cadherinmRNA表达呈显著负相关（r3=-0．99，r4=-0．98，P〈0．05）；Westernblot结果显示DSC中高表达ABCG2及P-糖蛋白，且与波形蛋白表达呈显著正相关（r1=0．98，r2=0．89，P〈0．05）；与E—cadherin蛋白表达呈负相关（r3=-0．47，r4=-0．33，P〈0．05）。结论化疗后残存乳腺癌组织ABCG2及P-糖蛋白与EMT相关标志物表达之间存在显著相关性，经历EMT可能是导致乳腺癌多药耐药的重要原因之一。Objective To explore the expression of breast cancer resistance protein （ABCG2） , p-glycoprotein （P-gp） in residual breast cancer tissue after chemotherapy and their correlation with epithelial mese,lchymal transition （EMT）. Methods Seventy-six cases of breast cancer were collected. The expression of ABCG2, P-gp and EMT markers E-cadherin and vimentin in residual breast cancer tissue after chemotherapy was detected by immunohistochemistry （ EnVision method）. MCF7 cells were divided into three group： untreated control group, positive control （TGF-[31 induced） group and drug surviving cells （DSC） group （selected viable MCF7 cells after docetaxel and epirubicin treatment）. The expression of EMT markers E-cadherin and vimentin was detected by immnnofluorescence. The mRNA and protein expression of ABCG2, P-gp and EMT markers were detected by reverse transcription-polymerase chain reaction （RT-PCR） and Western blot, respectively. Results Compared with breast cancer tissue before chemotherapy, ABCG2, P-gp and vimentin protein were highly expressed in residual breast cancer tissue after chemotherapy. The expression of ABCG2 and P-gp correlated positively with vimentin protein （ r1 =0. 97, P1 =0. 000; r2 = 0. 83, P2 = 0. 001 ） and negatively with E-cadherin protein （ r3 = - 0. 55, P3 = 0. 010; r4 = -0. 43, P4 = 0. 020） expression. RT-PCR results showed that ABCG2, P-gp and vimentin mRNA were highly expressed in residual breast cancer tissue after chemotherapy. The expressi^n ~f ABCG2 and P-gp mRNA correlated positively with vimentin mRNA （ rI = 0. 99, r2 = 0. 96, P 〈 0. 05 ） but negatively with E-cadherin protein （ r3 = 2- 0. 99, r4 = - 0. 98, P 〈 0. 05 ） ; Western blot showed that ABCG2, P-gp and vimentin protein were highly expressed in residual breast cancer tissue after chemotherapy. The expression of ABCG2 and P-gp protein correlated positively with vimentin protein （ r1 = 0. 98, r2 = 0. 89, P 〈 0. 05 ） and negatively with E-cadherin protein （ r3 = - O. 47

关 键 词：乳腺肿瘤 多药耐药相关蛋白质类 P糖蛋白 

分 类 号：R737.9[医药卫生—肿瘤]