Breast cancer resistance protein(BCRP/ABCG2):its role in multidrug resistance and regulation of its gene expression

Breast cancer resistance protein(BCRP)/ATP-binding cassette subfamily G member 2(ABCG2) is an ATP-binding cassette(ABC) transporter identified as a molecular cause of multidrug resistance(MDR) in diverse cancer cells.BCRP physiologically functions as a part of a self-defense mechanism for the organism;it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract,as well as through the blood-brain,placental,and possibly blood-testis barriers.BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use.Thus,BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs.Because BCRP is also known to be a stem cell marker,its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance,self-renewal(stemness),and invasiveness(aggressiveness),and thereby impart a poor prognosis.Therefore,blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers.Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR.Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1α,estrogen receptor,and peroxisome proliferator-activated receptor.Furthermore,alternative promoter usage,demethylation of the BCRP promoter,and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells.Finally,PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions.These biological events seem involved in a complicated manner.Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer.This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells,and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers.

Microarray analysis of gene expression profile of multidrug resistance in pancreatic cancer

Background Chemotherapy is the most frequently adopted adjuvant therapy of pancreatic ductal adenocarcinoma （PDAC）, but the development of drug resistance reduces its effectiveness. Clarification of the mechanism of multidrug resistance （MDR） development in PDAC is needed to improve the therapeutic effect of chemotherapy. This study was aimed to investigate the molecular mechanism of MDR of PDAC and to identify genes associated with MDR development.Methods The gene expression profiles of cell line SW1990 and three drug-selected pancreatic chemoresistant sub-lines, SW1990/5-Fu, SW1990/ADM and SW1990/GEM, were obtained using an oligonucleotide microarray （Affymetrix HG U133 2.0 plus） that contained approximately 38 000 human genes. The microarray results were validated by real-time quantitative polymerase chain reaction and Western blot analysis.Results There were 165 genes and expressed sequence tags, some of which have never been linked to drug resistance, that were up- or down-regulated at least 2-fold in all resistant sub-lines when compared with SW1990. According to Gene Ontology annotation, differentially expressed genes related to MDR in pancreatic cancer belong to many functional families and with diverse biological processes. Genes related to antioxidant activity, apoptosis, the cell cycle, signal transduction and intracellular adhesion may undergo epigenetic changes preceding MDR development. A hierarchical clustering was conducted and several interesting clusters were discovered that may be primarily related to cell cycle and developmental regulation. A prediction rule was built from the expression profiles of 117 genes after support vector machine （SVM） analysis, and the prediction result was examined by cytotoxic testing. As a result, a differential gene expression pattern was constructed in multidrug resistant pancreatic cancer cells. Conclusions The findings of this study prove that construction of a chemoresistance prediction rule, based on gene expression patterns, is practical. These data provide new insights into the molecular mechanism of pancreatic cancer MDR develonment And mav be useful for the detection and treatment of MDR in pancreatic cancer patients.

GENE EXPRESSION PROFILING IN MULTIDRUG RESISTANT KB CELLS USING cDNA MICROARRAYS

Objective: A single mechanistic pathway cannot explain the genesis of drug resistance in cancer. Drug resistance in cancer is a major obstacle to successful chemotherapy. KB cells provide a useful starting point for selection of the multidrug resistant (MDR) cell lines. Methods: We used cDNA microarrays containing 12,720 sequences of known genes, expressed sequence tags and unknown clones to monitor gene expression profiles in MDR KB cells. Results: Preliminary data analysis showed that 18 genes were up-regulated and 18 genes were down-regulated by comparison of expression patterns between KB 3-1 and MDR KB-V1 cells. Furthermore, the highly over-expressed CGA, CLU genes in MDR KB-V1 cell were verified with conventional Northern blot analysis. These genes contain information predictive of drug resistance of cancer cells. Conclusion: Our study demonstrates that genome-wide gene expression profiling by using cDNA microarray technique is a valuable approach in obtaining molecular mechanism of drug resistance in cancer cells.

ESTABLISHMENT OF CRITERIA FOR MEASURING MDR-1 GENE EXPRESSION LEVEL IN BREAST CANCER BY RT-PCR

Objective: To formulate criteria of multidrug resistance (mdr1) gene expression for predicting chemotherapy response and prognosis. Methods: Using reverse transcriptionpolymerase chain reaction (RTPCR) assay, the expression of mdr1 gene in 82 breast cancer samples were detected. Results: The data were treated by statistic analysis system (SAS)singlevariate analysis. It showed that the level of mdr1 gene expression clearly deviated from normal to right distribution (P<0.0001), and thus might be divided by quantiles P50 (mdr1/β 2MG=0.2) and P75 (mdr1/β 2MG=0.6), which were taken as the preliminary criteria for analyzing 56 patients' chemosensitivity to ADM、VDS and VCR in vitro and 32 relapsed metastatic patients' chemotherapy response in vivo, seperately. When mdr1/( 2MG(0.2, the ratios of resistance gradually escalated, but there were about 30%～50% of the cases who showed sensitive to the drugs in vitro and effective to chemotherapy in vivo. When mdr1/β 2MG≥0.6, the most of patients showed drug resistance both in vitro and in vivo. Conclusion: According to the abovementioned results, criteria of evaluating mdr1 gene expression level was formulated: the mdr1/β 2MG<0.2 (P50) was considered as negative expression, the ratio≥02～<0.6 (P75) was weakly positive expression, ≥0.6 was strongly positive expression. This indicated that different levels of mdr1 gene expression may reflect objectively drug resistance in vitro and chemotherapy response in vivo.

Congenital expression of mdr-1 gene in tissues of carcinoma and its relation with patho morphology and prognosis

AIM To detect the congenital expression patterns of mdr 1 gene in commonly encountered malignant tumors in clinic, and the relationship between the expression of mdr 1 gene and the prognostic morphology in esophageal carcinomas. METHODS A total of 151 resected samples of malignant tumors without preoperative treatment were taken from Anyang City Tumor Hospital. The congenital expression of their mdr 1 gene was detected with reverse transcription polymerase chain reaction (RT PCR) and was compared with each other. The positive incidence of mdr 1 gene in 46 samples of esophageal carcinoma was compared with their differentiated grades, TNM stages and macroscopic types, and the precautions and advantages of RT PCR were evaluated. RESULTS All the 151 samples were confirmed to be malignant histopathologically, including cancers of stomach and gastric cardia (n =51), esophagus ( n =46), colorectum ( n =16), breast ( n =15), thyroid ( n =10), lung ( n =9), uterine cervix ( n =24). The positive expression rate of their mdr 1 gene was 33 3%, 37%, 31 3%, 13 2%, 40%, 55%, and 0% respectively. All the 46 samples of esophageal carcinoma were pathologically confirmed to be squamous cell carcinoma. The total expression rate of their mdr 1 gene was 37% (17/46), 35% (6/17), 40% (8/20), and 33% (3/9) for differentiation grade Ⅰ, Ⅱ and Ⅲ respectively. The expression rate of TNM classification was 33% (6/18), 40% (5/12) and 37% (6/16) in stage Ⅱa, Ⅱb and Ⅲ. The expression rate was 33% (3/9) in ulcerous type, 37% (3/8) in constrictive one, 33% (5/15) in fungoid one, and 40% (6/14) in medullary one. No statistically significant difference was found. CONCLUSION Compared with other methods, RT PCR is more simple, reliable and accurate in detecting mdr 1 gene expression in tissues of tumor. The overexpression of mdr 1 gene in these neoplasms suggested that cases should be handled differently for chemotherapy with rational use of drugs. Excision is the chief treatment for carcinoma of esophagus. The expression of mdr 1 gene in tissues of esophageal cancer is correlated with the parameters of tumor molecular biology which are independent of histopathological morphology.

Quantitative detection of peripheral MDR genes in breast cancer before chemotherapy and their clinical significances

Objective： To explore expressions of multidrug resistance gene （MDR） product P170 and peripheral blood MDR1 mRNA in breast cancer tissue and their clinical significances. Methods： Fluorescent quantitative RT-PCR and immunohistochemistry were used to detect peripheral blood MDR1 mRNA before chemotherapy in breast cancer tissue samples from 32 cases with P170 positive （trial group） and 11 cases with P170 negative （control group）. Results： There were 14 cases （43.75%） peripheral blood MDR1 mRNA positive and 18 cases （56.25%） negative in 32 cases P170 positive breast cancer patients, while there were 6 cases （54.55%） peripheral blood MDR1 mRNA positive and 5 cases （45.45%） negative in 11 cases P170 negative breast cancer patients; there wasn＇t a significance difference with peripheral blood MDR1 mRNA express rate in P170 positive （43.75%） group and P170 negative （54.55%） group （x2 = 0.383, P 〉 0.05）. There were 12 cases （37.50%） Her-2 positive and 20 cases （62.50%） negative in P170 positive group; there were 2 cases （18.18%） Her-2 positive and 9 cases （81.82%） negative in P170 negative group; there wasn＇t a significance difference with Her-2 positive rate in P170 positive group （37.50%） and P170 negative （18.18%） group （χ^2= 1.391, P 〉 0.05）. There were 13 cases （40.63%） ER positive and 19 cases （59.37%） negative in P170 positive group; there were 7 cases （63.64%） ER positive and 4 cases （36.36%） negative in P170 negative group; there wasn＇t a significance difference with ER positive rate in P170 positive group （40.63%） and P170 negative （63.64） group （χ^2 = 1.742, P 〉 0.05）. There were 20 cases （62.50%） PR positive and 12 cases （37.50%） negative in P170 positive group; there were 4 cases （36.36%） PR positive and 7 cases （63.64%） negative in P170 negative group; there wasn＇t a significance difference with PR positive rate in P170 positive group （62.50%） and P170 negative （36.36%） group （χ^2 = 2.267, P 〉 0.05）. There were 9 cases （28.12%） with lymphaden metastasis and 23 cases （71.88%） without lymphaden metastasis in P170 positive group; there were 5 cases （45.45%） with lymphaden metastasis and 6 cases （54.55%） without lymphaden metastasis in P170 negative group; there wasn＇t a significance difference with lymphaden metastasis rate in P170 positive group （28.12%） and P170 negative （45.45%） group （χ^2 = 1.120, P 〉 0.05）. Conclusion： 1） There were possibly MDR expressing infrequently in carcinoma tissue and peripheral blood before chemotherapy. 2） FQ-RT-PCR for detecting of peripheral blood MDR1 mRNA is special, sensitive and reliable. It can be used as new molecular biology diagnostic maker dynamic detecting peripheral blood MDR1 mRNA for regulating chemotherapy proposal and elevating chemotherapy effect.

5种耐药基因在成人常见恶性肿瘤中的表达特点

目的:通过对成人肝癌、肺癌、胃癌、肠癌、乳腺癌、卵巢癌5种耐药基因蛋白的检测,了解常见恶性肿瘤组织耐药基因表达的一般规律和特点。方法:应用SP免疫组织化学法检测120例成人常见肿瘤标本P-gp、MRP、LRP、GST-π、Topo-Ⅱ的表达。结果:1.在6种常见肿瘤中P-gp、MRP、LRP、GST-π相对高表达,而Topo-Ⅱ相对低表达。2.肝癌的5种耐药基因蛋白表达均偏高。3.2种和2种以上耐药基因的共表达率达95.83%,其中5种耐药基因共表达率达21.67%。结论:P-gp、MRP、LRP、GST-π、Topo-Ⅱ均不同程度的参与了肿瘤耐药机制,临床上可作为指导用药的综合指标,实现个体化化疗。

急性白血病中MDR1 MRP和bcl-2基因表达及其临床意义

目的:研究多药耐药基因(MDR1)、多药耐药相关蛋白基因(MRP)和调控细胞凋亡有重要作用的基因(bcl-2)在急性白血病(AL)中的表达以及它们与临床耐药之间的关系。方法:采用地高辛掺入的半定量逆转录聚合酶链反应(RT-PCR)及常规RT-PCR方法检测了54例急性白血病患者和10例正常人骨髓单核细胞中基因的表达情况。结果:54例AL中MDR1/MRP/bcl-2三基因表达阳性率为16.7%(9/54),MDR1/MRP/bcl-2三基因表达均阴性,发生频率为46.3%(25/54)。46例资料完整的白血病患者中三基因表达均阴性者80.0%缓解(CR),MDR1/MRP或MDR1/MRP/bcl-2共表达者无1人CR(P<0.01)。单基因分析表明MDR1、MRP、bcl-2基因表达阳性率分别为28.3%、41.3%和47.8%,其中MDR1阳性者CR率7.7%,明显低于MDR1阴性者CR率72.7%(P<0.01);MRP阳性CR率21.1%,明显低于阴性CR率77.8%(P<0.01);bcl-2阳性CR率36.4%,亦低于阴性CR率70.8%(P<0.05)。结论:MDR1/MRP或MDR1/MRP/bcl-2共表达的患者不易获得CR,白血病患者的耐药除了与MDR1高表达密切相关外,还与非P-糖蛋白(P-gp)介导的MRP及bcl-2表达等因素相关。

83例大肠癌多药耐药基因的检测

目的:研究复发及多源发大肠癌多药耐药基因的表达。方法 :采用逆转录 -多聚酶链式反应 (RT -PCR)技术对 83例大肠癌多药耐药 (mdr - 1)基因进行了检测。结果 :原发大肠癌mdr - 1基因表达率 30 .9%(12 / 42 ) ,复发大肠癌mdr- 1基因表达率 6 1.3% (19/ 31) ,两者有显著差异 (P <0 .0 5 )。多源发大肠癌mdr -1基因阳性表达率 6 0 % (6 / 10 )。mdr- 1基因表达的阳性和阴性与耐药与否的总符合率达 10 +16 / 31(P <0 .0 5 )。结论 :大肠癌组织mdr- 1基因的表达水平 ,这对正确判断病人耐药能力的高低 ,合理术后化疗 。

多药耐药基因在大肠癌中的检测及其临床意义

我们利用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）技术定量分析了５４例大肠癌患者多药耐药基因（ＭＤＰ１）表达水平，探讨其与临床化疗的相关性。初步检测结果表明：大肠癌化疗疗效与ＭＤＲＩ的表达水平有关，未经化疗的患者ＭＤＲＩ呈低水平表达（＜０．５）；化疗后的患者ＭＤＲＩ均呈高水平表达（＞０．５），而且随着化疗疗程的增加ＭＤＲＩ的表达水平有增加的趋势（０．５～０．９７）。化疗前后ＭＤＲＩ的表达水平具有极显著的差异（Ｐ＜０．００１）；同时还发现同一病理类型分化程度不同的癌肿ＭＤＲＩ的表达水平也不同，高分化腺癌要明昆高于中、低分化腺癌（Ｐ＜０．０１）。

逆转录病毒转染法建立耐药性人膀胱癌细胞系

目的 建立高效、稳定的人膀胱癌多药耐药性细胞模型。方法 应用逆转录病毒转染法建立人膀胱癌耐药性细胞模型 ;MTT法检测细胞系在不同化疗药物作用下的生存率 ,免疫组化检测肿瘤的 P- GP表达 ,原位杂交检测肿瘤细胞 mdr1m RNA的表达量 ,PCR检测 mdr1基因转移至细胞基因组片段。结果 转基因细胞系对阿霉素、秋水仙素的耐药性分别提高 8倍和 2 1倍 ,免疫组化示转基因细胞系 P-GP表达量增强 ,原位杂交结果示肿瘤细胞内 m dr1m RNA的表达量明显增加 ,PCR表明基因转移后细胞内能扩增出mdr1片段。结论 逆转录病毒转染法 ,是建立人膀胱癌多药耐药性细胞模型的一种较理想的方法。

盐酸千金藤素逆转EAC/ADR细胞多药耐药性的作用及其机制

目的研究盐酸千金藤素对艾氏腹水癌耐药细胞株EAC/ADR多药耐药性的逆转作用及其与核因子κB (NF κB)的关系,探讨其作用机制。方法 MTT法、小鼠移植瘤模型实验观察盐酸千金藤素体外和体内逆转细胞多药耐药性的作用;Dot ELISA法检测细胞核NF κB水平及药物作用后的变化。结果 盐酸千金藤素体外能逆转 EAC/ADR细胞的耐药性,逆转倍数为13倍;体内能延长荷瘤小鼠的生存时间,生命延长率为75.37%;并能降低 EAC/ADR细胞中NF κB的持续性活性及化疗药物对其的激活。结论 盐酸千金藤素具有逆转多药耐药性的作用, 其机制可能与抑制NF κB的活性有关。

多药耐药相关蛋白基因、肺耐药蛋白基因在肝细胞癌中的表达及临床意义

目的 研究多药耐药相关蛋白基因 (MRP)和肺耐药蛋白基因 (LRP)在肝细胞癌 (HCC)中的表达及其与临床的关系。方法 采用SP免疫组化和PCR技术检测 5 4例HCC和 2 4例癌旁组织及 1 2 例肝炎后肝硬化组织中的两种基因表达。结果 MRP和LRP在 3种组织中均有表达,HCC组织中其基因表达显著高于其他组织 (P< 0. 0 5 )。HCC中两种基因表达呈正相关 (r= 0. 3 1 2, P <0. 0 5; r= 0. 3 2 8, P< 0. 0 5 );其表达与HCC的分化程度有关 (P< 0. 0 5 )。并且其表达阳性组患者化疗后AFP有效率和平均生存期分别高于和长于阴性组 (P< 0. 0 5 ),但LRP与平均生存期无关 (P> 0. 0 5 )。结论 HCC多药耐药 (MDR)与两种基因表达有关,起源于内源性耐药;检测其表达对预测化疗耐药具有指导意义;MRP可能与预后有关。

P-gp及对抗P-gp介导多药耐药的研究现状

P-糖蛋白在多药耐药中起着重要的作用。本文就P-gp的蛋白结构、作用机制及其与多药耐药的关系以及对抗P-gp介导的MDR的现状做了简要介绍。总之,一方面要继续开发高效的P-gp抑制剂,同时,又要考虑过度抑制P-gp可能会带来不良影响;在抑制P-gp的同时,还要兼顾对其它耐药机制的抑制,只有这样,才能在临床上充分解决多药耐药的问题。

急性白血病细胞的乳腺癌耐药蛋白基因表达与化疗耐药的关系

为了探讨急性白血病 (AL)患者乳腺癌耐药蛋白 (BCRP)基因表达与化疗耐药及预后的关系 ,本研究应用半定量逆转录 -聚合酶链反应 (RT PCR)的方法 ,以 β2 微球蛋白 (β2 MG)作阳性对照 ,检测了 72例AL患者的白血病细胞及 15名正常对照者白细胞的BCRPmRNA的表达 ,将BCRP/ β2 MG≥ 0 .5定为BCRP基因表达阳性。结果显示 :初治组BCRP基因表达的阳性率为 37.6 % ,BCRP基因表达阳性与BCRP基因表达阴性患者的首次完全缓解 (CR1)率分别为 31.6 %和 79.3% (P =0 .0 0 1) ;临床耐药组 (NR组 )与化疗敏感组 (CR组 )BCRP基因的表达水平分别为 0 .96 2± 0 .4 2 6和 0 .315± 0 .2 96 (P =0 .0 0 0 1) ;复发 /难治组BCRP基因表达水平显著高于初治组 (P =0 0 0 2 5 ) ;正常对照组及长期生存组BCRP基因表达的水平较低 ;BCRP基因表达与FAB分型有关。结论 :BCRPmRNA过度表达可导致临床化疗耐药 ,是AL患者 (除M3 外 )预后的重要不利因素。

p53 和 c-myc 异常表达与胃癌细胞多药耐药性关系的研究

应用ＬＳＡＢ免疫组织化学方法研究６７例胃标本中ｐ５３和ｃｍｙｃ的表达与多药耐药性（ＭＤＲ）的关系。结果显示：本组胃癌中ｐ５３阳性３２例，阳性率４７８％；ｃｍｙｃ阳性３７例，阳性率５５２％；Ｐｇｐ阳性３９例，阳性率５８２％。ｐ５３的异常表达与ｍｄｒ１基因表达呈显著正相关（ｒ＝０６３，Ｐ＜００５），而ｃｍｙｃ和ｍｄｒ１的表达无明显相关。提示ｐ５３异常表达可增加ｍｄｒ１基因的表达，从而使胃癌细胞获得ＭＤＲ表型。

外源性TNF-α基因克服多药耐药性的初步研究

目的：探索外源性细胞因子 TNF-α基因克服多药耐药（ multidrug resistance,MDR）的新途径。方法：以重组逆转录病毒为载体，将 TNF-α基因导入具 MDR表型的人乳腺癌细胞系 MCF- 7/Adr，经 G418抗性筛选获阳性克隆 MCF- 7/Adr- TNF1与 MCF- 7/Adr- TNF2。以 PCR和 ELISA法检测目的基因的整合与表达。细胞计数法观察细胞生长速度的改变 , MTT法检测外源性 TNF-α基因的逆转 MDR作用，流式细胞仪分析细胞内 ADR积累的变化。结果： MCF- 7/Adr- TNF1与 MCF- 7/Adr- TNF2细胞中有 TNF-α基因的整合和表达，病毒上清中 TNF-α含量分别为 1 737 pg/ml（ 106 cells/48 h）、 2 875 pg/ml。与阴性对照细胞相比， MCF- 7/Adr- TNF1与 MCF- 7/Adr- TNF2细胞的生长速度明显减慢，生长抑制率分别为 32.4％、 54.8％，对 ADR的耐药性明显降低，耐药逆转倍数分别为 5.2倍、 19.3倍，细胞内 ADR的积累明显增加。结论：外源性 TNF-α基因的导入能有效克服耐药性，增加细胞内药物的积累为其逆转耐药性的主要机制。

MCF-7/Adr细胞mdr-1基因启动子甲基化和组蛋白乙酰化状态与多药耐药的关系(英文)

目的:分析MCF-7/Adr及MCF-7细胞mdr-1基因启动子甲基化和组蛋白乙酰化状态,初步探讨乳腺癌多药耐药的表观遗传机制。方法:用甲基化敏感PCR技术检测两个细胞系mdr-1基因启动子甲基化状态。实时定量PCR技术检测DNA甲基转移酶(DNA methyltransferases,DNMTs)mRNA及组蛋白去乙酰化酶(histone deacetylases,HDACs)mRNA的表达。光密度值法检测组蛋白H3和H4乙酰化水平。结果:MCF-7细胞mdr-1基因启动子呈现高甲基化,MCF-7/Adr细胞mdr-1基因启动子呈现低甲基化。与MCF-7细胞比较,MCF-7/Adr细胞DNMT1,DNMT3a及DNMT3bmRNA表达显著下降(P<0.05)。MCF-7/Adr细胞组蛋白H3和H4乙酰化水平较MCF-7细胞明显升高(P<0.01)。与MCF-7细胞比较,MCF-7/Adr细胞HDAC1,HDAC2,HDAC7及SIRT1mRNA的表达显著下降(P<0.01)。结论:mdr-1基因启动子低甲基化、组蛋白H3和H4高乙酰化、DNMTs mRNA及HDACs mRNA低表达可能是介导MCF-7/Adr细胞MDR形成的重要表观遗传学因素。

三物白散加味方影响肿瘤多药耐药基因表达实验研究

观察三物白散加味方对肿瘤多药耐药(MDR)基因表达的影响。以三物白散加味方含药血清加入人胃癌SGC-7901细胞中,观察MDR基因表达的变化。结果:三物白散加味方可降低人胃癌SGC-7901细胞MDR基因表达率。提示三物白散加味方临床不易产生多药耐药,并可作为MDR逆转剂使用。

MDR1、BCRP和LRP基因在乳腺癌组织中的表达及其意义

目的探讨多药耐药基因(MDR1)、乳腺癌耐药蛋白(BCRP)及肺耐药蛋白(LRP)mRNA在乳腺癌组织中的表达及其相互关系,分析它们与乳腺癌临床病理特征的关系。方法采用RT-PCR方法检测2007年1月至2007年12月在宁夏医科大学附属医院手术切除的42例乳腺癌组织、42例癌旁组织及50例乳腺良性病变中MDR1、BCRP和LRP mRNA的表达。结果乳腺癌组织中MDR1、BCRP、LRP mRNA的阳性表达率分别为40.47%、38.09%及61.90%,与癌旁组织及乳腺良性病变组织相比阳性表达率均有统计学差异(P<0.05)。MDR1mRNA表达与绝经状况呈完全正相关(r=0.398,P<0.01),与腋窝淋巴结状况呈完全正相关(r=0.398,P<0.01);BCRP mRNA表达与腋窝淋巴结状况呈正相关(r=0.355,P<0.05);LRP mRNA表达与绝经状况、年龄、腋窝淋巴结状况及肿瘤大小之间均无相关性(P>0.05);MDR1mRNA和BCRP mRNA表达呈正相关(r=0.652,P<0.01),LRP mRNA与MDR1mRNA表达无相关性(r=0.147,P>0.05);LRP mRNA和BCRP mRNA表达无相关性(r=0.111,P>0.05)。2个耐药基因共表达率为47.61%,2种或3种耐药基因共表达率为61.89%。结论乳腺癌组织中存在耐药基因MDR1、BCRP和LRP的表达,单基因和多基因协同作用,以多基因共表达为主;检测MDR1和BCRP基因表达水平可辅助临床判断乳腺癌患者的预后。