P-gp基因突变与乳腺癌多药耐药的研究  

Relationship between P - gp gene mutation and multi - drug resistance of breast cancer

作　　者：郭良峰[1] 袁建辉[2] 何劲松[1] 王先明[1] 伍建春[1] 李戎[1] 朱国献[1] 佟建蒙[1] 刘瑾琨[1] 

机构地区：[1]广东省深圳市第二人民医院乳腺外科,深圳518035 [2]深圳市疾病预防控制中心

出　　处：《中原医刊》2007年第11期1-3,共3页Central Plains Medical Journal

基　　金：国家自然科学基金青年基金（2005）

摘　　要：目的研究乳腺癌中P-gp基因的突变与其多药耐药的关系。方法采用MTT法检测52例临床乳腺癌标本对四种抗癌药物的敏感性,PCR扩增P-gp基因中最常发生突变的250个碱基进行单链构象多态性（SSCP）分析,根据SSCP的结果,挑取12个样本,将其核苷酸序列与野生型P-gp基因进行比较。结果52例乳腺癌组织中有8例对4种抗癌药物都敏感;对1种抗癌药物耐受的有19例,只有1例P-gp基因发生点突变;对2种抗癌药物耐受的有16例,其中有2例P-gp基因发生了点突变;对3种抗癌药物耐受和4种抗癌药物耐受的乳腺癌组织分别是7例和2例,它们的P-gp基因都发生了点突变。在这12例标本中,891gly（GGC→GAC）asp突变为5例,1145位his（CAC→TAC）tyr的突变为7例。结论P-gp基因突变介导乳腺癌的多药耐药,P-gp基因产物891位gly（GGC→GAC）asp和1145位his（CAC→TAC）tyr的突变与乳腺癌多药耐药的关系密切。Objective To study the relationship between P - gp gene mutation and multi - drug resistance of breast cancer. Methods The sensitivity of kinds of anti - cancer drugs to 52 human breast cancer samples was checked by MTT method. According to the results from single strain conformation polymorphism （SSCP） analysis of PCR amplified 250 common mutable base pairs within P -gp gene,the mucleitide sequence of 12 interested samples was compared with that of wild type P - gp gene. Results In 52 samples, 8 cases were sensitive to all the 4 kinds of drugs. Nineteen cases, in which only one underwent P- gp gene mutation,were resistant to one kind of drug; 16 cases, in which the mutation occurred in 2 cases,were resistant to 2 kind of drugs;7 and 2 cases,in whkich all the cases underwent the same gene mutation, resistant to 3 and 4 kinds of drugs respectively. Among the 12 cases,5 cases of 891gly mutated to asp （GGC →GAC） ,and the other 7 cases of 1145 his mutated to tyr （CAC→TAC）. Conclusion There is close relationship between P - gp gene point mutation（891 gly to asp, 1145 his to tyr）and multi- drug resistance of human breast cancer.

关 键 词：乳腺癌 多药耐药 点突变 聚合酶链反应 单链构象多态性分析 

分 类 号：R737[医药卫生—肿瘤]