GOLM1表达水平与ER阳性乳腺癌对内分泌治疗敏感性的关系  

Relationship between GOLM1 expression level and sensitivity to endocrine therapy in ER-positive breast cancer

作　　者：刘香娟 张家宏 张剑 臧红艳[1] Liu Xiangjuan;Zhang Jiahong;Zhang Jian;Zang Hongyan(Department of Breast Surgery,Yantai Yantaishan Hospital,Yantai 264003,China;Department of First General Surgery,Yantai Penglai People's Hospital,Yantai 265600,China)

机构地区：[1]烟台市烟台山医院乳腺外科,烟台264003 [2]烟台市蓬莱人民医院普外一科,烟台265600

出　　处：《中华内分泌外科杂志》2023年第4期499-503,共5页Chinese Journal of Endocrine Surgery

基　　金：烟台市科技创新发展计划(2021YD049)。

摘　　要：目的探讨高尔基膜蛋白1(golgimembrane protein1,GOLM1)表达水平与雌激素受体(estrogen receptor,ER)阳性乳腺癌对内分泌治疗敏感性的关系。方法建立他莫昔芬(tamoxifen,TAM)耐药的ER阳性乳腺癌细胞,分析并检测细胞中GOLM1表达水平。调控细胞中GOLM1表达水平,MTT与集落形成实验分别检测GOLM1表达变化对细胞增殖与集落形成的影响。Westernblot检测GOLM1表达变化对细胞中耐药蛋白P-gp、MRP1表达的影响。募集内分泌治疗的乳腺癌患者与未经内分泌治疗的患者,将其分为GOLM1高表达组与低表达组,观察GOLM1表达水平对两组生存率的影响。结果集落形成实验显示经过他莫昔芬治疗,他莫昔芬耐药的MCF-7R细胞的集落形成能力显著高于敏感的MCF-7细胞(均P<0.05)。较MCF-7细胞(1.00±0.10)和MCF-7R细胞(2.31+0.18)中GOLM1表达水平升高(t=11.02,P<0.001)。在MCF-7R细胞中敲减GOLM1,细胞的增殖能力与集落形成能力均降低,耐药蛋白P-gp、MRP1的表达也降低(均P<0.05)。经内分泌治疗的患者,G0LM1高表达患者生存率低于低表达患者生存率(x=5.45,P=0.020)。未经内分泌治疗的患者,GOLM1高表达患者与低表达患者的生存率无显著差异(X=1.49,P=0.223)。结论GOLM1高表达与ER阳性乳腺癌患者对内分泌治疗敏感性降低显著相关.Objective To investigate the relationship between Golgi membrane protein 1(COLM1)expression and the sensitivity of estrogen receptor(ER)positive breast cancer to endocrine therapy.Methods Tamoxifen(TAM)-resistant ER-positive breast cancer cells were established,and the expression of GOLMI in these cells was detected.The expression level of COLM1 in the cells was regulated,and the effects of GOLM1 expression on cell proliferation and colony formation were detected by MTT and colony formation assay,respectively.Western blot was used to detect the effect of GOLM1 expression on the expression of drug resistance proteins P-gp and MRP1.Breast cancer patients recruited for endocrine therapy and patients without endocrine therapy were divided into high GOLM1 expression group and low GOLM1 expression group,and the effect of GOLM1 expression level on the survival rate of the two groups of patients was observed.Results Colony formation assay showed that after TAM treatment,the colony formation ability of TAM-resistant MCF-7 cells was significantly higher than that of TAM-sensitive McF-7 cells(all P<0.05).The expression level of COLM1 in MCF-7R cells(2.31+0.18)was higher than that in MCF-7 cells(1±0.10)(t=11.02,P<0.001).Knockdown of GOLM1 in MCF-7R cells decreased the cell proliferation and colony formation ability,and the expression of drug resistance proteins P-gp and MRP1 also decreased(all P<0.05).The survival rate of patients with high GOLM1 expression was lower than that of patients with low COLM1 expression after endocrine therapy(x^(2)=5.45,P=0.020).In patients without endocrine therapy,there was no significant difference in survival between patients with high and low GOLM1 expression(=1.49,P=0.223).Conclusion High expression of GOLMI is significantly associated with decreased sensitivity to endocrine therapy in ER-positive breast cancer patients.

关 键 词：乳腺癌 高高尔基膜蛋白1 他莫昔芬 此雌激素受体 

分 类 号：R737.9[医药卫生—肿瘤]