[化疗后残留乳腺癌组织中ABCG2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 epithelial-mesenchymal transition].
作者信息
Qu Hongbo, Fang Li, Duan Lili, Long Xiaobin
机构信息
Department of Breast and Thyroid and Vascular Surgery of Chen Zhou First People Hospital in Hunan Province, ChenZhoucity 423000, China.
E-mail:
出版信息
Zhonghua Bing Li Xue Za Zhi. 2014 Apr;43(4):236-40.
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 mesenchymal 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-β1 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 immunofluorescence. 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 expression of ABCG2 and P-gp mRNA correlated positively with vimentin mRNA (r1=0.99, r2=0.96, P<0.05) but negatively with E-cadherin protein (r3=-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=-0.47, r4=-0.33, P<0.05).
CONCLUSIONS
The expression of resistance-associated proteins in the residual breast cancer tissue after chemotherapy is significantly correlated with EMT. The expression of EMT profile may be one of important mechanisms for multidrug resistance in breast cancer.
目的
探讨乳腺癌耐药蛋白（ABCG2）、P-糖蛋白（P-gp）在化疗后残留乳腺癌组织中的表达及其与上皮间质转化（EMT）的相关性。
方法
收集76例乳腺癌病例。采用免疫组织化学（EnVision法）检测化疗后残留乳腺癌组织中ABCG2、P-gp及EMT标志物E-钙黏蛋白和波形蛋白的表达。将MCF7细胞分为三组：未处理对照组、阳性对照组（转化生长因子-β1诱导组）和药物存活细胞组（多西他赛和表柔比星处理后筛选出的存活MCF7细胞）。采用免疫荧光法检测EMT标志物E-钙黏蛋白和波形蛋白的表达。分别采用逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测ABCG2、P-gp及EMT标志物的mRNA和蛋白表达。
结果
与化疗前乳腺癌组织相比，化疗后残留乳腺癌组织中ABCG2、P-gp及波形蛋白蛋白高表达。ABCG2和P-gp的表达与波形蛋白蛋白呈正相关（r1 = 0.97，P1 = 0.000；r2 = 0.83，P2 = 0.001），与E-钙黏蛋白蛋白呈负相关（r3 = -0.55，P3 = 0.010；r4 = -0.43，P4 = 0.020）。RT-PCR结果显示，化疗后残留乳腺癌组织中ABCG2、P-gp及波形蛋白mRNA高表达。ABCG2和P-gp mRNA的表达与波形蛋白mRNA呈正相关（r1 = 0.99，r2 = 0.96，P < 0.05），与E-钙黏蛋白蛋白呈负相关（r3 = -0.99，r4 = -0.98，P < 0.05）；蛋白质免疫印迹法显示，化疗后残留乳腺癌组织中ABCG2、P-gp及波形蛋白蛋白高表达。ABCG2和P-gp蛋白的表达与波形蛋白蛋白呈正相关（r1 = 0.98，r2 = 0.89，P < 0.05），与E-钙黏蛋白蛋白呈负相关（r3 = -0.47，r4 = -0.33，P < 0.05）。
结论
化疗后残留乳腺癌组织中耐药相关蛋白的表达与EMT显著相关。EMT特征的表达可能是乳腺癌多药耐药的重要机制之一。
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