P-gp基因突变与乳腺癌多药耐药分子机制的研究

Study on P-gp gene mutation and molecular mechanism of multi-drug resistance of breast cancer

目的探讨P-糖蛋白(P-gp)基因突变与乳腺癌多药耐药的关系。方法本组自2004年3月至2006年4月采用MTT法检测52例乳腺癌标本对四种化疗药物的敏感性,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,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8例对四种抗癌药物均敏感,无P-gp基因突变;19例对一种抗癌药物耐受,其中仅一例P-gp基因发生点突变;16例对两种抗癌药物耐受,其中两例发生P-gp基因点突变;7例和2例分别对三种抗癌药物耐受和四种抗癌药物耐受,它们的P-gp基因都发生了点突变。P-gp基因突变位点分别为891gly位(GGC→GAC)asp和1145位his(CAC→TAC)tyr。结论P-gp基因突变介导乳腺癌多药耐药,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密切相关。

Objective To investigate the relationship between P-gp gene mutation and multidrug resistance of breast cancer. Methods From March 2004 to April 2006, 52 cases of breast cancer samples were detected to sensitivity of 4 kinds of chemotherapeutic drugs by MTF. Among the most common mutation of PCR amplified P-gp genes, analysis of single strand conformation polymorphism was done in 250 base. And its nucleotied sequence and wild type P-gp were compared. Results In the 52 cases of breast cancer tissues,4kind of anticarcinogen were sensitive in 8 cases and no mutation of P-gp gene was found. 1 kind of anticarcinogen resistance was in 19 cases of among them, P-gp gene point mutation was occurred only 1 case. 16 cases had resistivity to 2 kinds of anticarcinogen and among them, P-gp gene point mutations were occurred in 2cases. 7 and 2 cases had resistivity to 3 and 4 kinds of anticarcinogen respectively and their P-gp gene point mutation were happened. The P-gp gene mutation points were in the site of 891 （GGC→GAC） asp and 1145 his （CAC→TAC） tyr respectively. Conclusion P-gp gene mutation may induce multi-drug resistance of breast cancer. Mutation of P-gp gene product of 891 site gly（GGC→GAC） asp and 1145 site his （CAC→TAC） tyr are closely correlated with multi-drug resistance of breast cancer.