摘要目的 探讨哺乳动物雷帕霉素靶蛋白( mTOR)信号通路中mTOR及其下游分子4E结合蛋白1(4EBP1)及核糖体S6蛋白激酶1(S6K1)在乳腺癌组织中的表达和临床意义.方法 应用免疫组织化学方法检测116例浸润性乳腺癌及其癌旁组织中磷酸化的mTOR与4EBP1及S6K1的表达,分析三者表达的相关性,及其与患者年龄、肿瘤大小、腋淋巴结转移状况、组织学分级、临床分期以及雌激素受体(ER)、孕激素受体(PR)、原癌基因表皮生长因子受体2(Her-2)等临床病理参数之间的关系.结果 (1) p-mTOR、p-4EBP1和p-S6K1在乳腺癌组织中的阳性表达率分别为68.1％、65.5％、59.5％,显著高于其在癌旁组织中的表达,差异有统计学意义(P＜0.05).(2)p-mTOR与p-4EBP1及p-S6K1的表达明显相关(r=0.458,P＜0.05;r =0.383,P＜0.05).(3)在腋淋巴结转移患者中p-mTOR、p-4EBP1、p-S6K1的阳性表达明显高于无淋巴结转移组,差异有统计学意义(P＜0.05),而三者的表达与其他各临床病理参数无明显相关.结论 mTOR信号通路中mTOR及其下游分子4EBP1及S6K1的激活与乳腺癌的发生相关,并对促进腋窝淋巴结转移有一定作用.同时作为信号通路中的上游分子,mTOR对其下游的4EBP1及S6K1具有调控作用.

abstractsObjective To discuss the expression of p-mammalian target ot rapamycin (mTOR),p-4E binding protein 1 (4EBP1) and p-ribosomal protein S6 kinase ( S6K1 ) in breast carcinoma and their relationship with clinicopathological parameters.Methods The expression of p-mTOR,p-4EBP1 and p-S6K1 in 116 cases of breast carcinoma and tumor adjacent tissues was detected by using immunohistochemistry,and the correlation among them as well as their relationship with clinicopathological parameters.Results ( 1 ) The expression rate of p-mTOR,p-4EBP1 and p-S6K1 in breast carcinoma was 68.1％,65.5％,and 59.5％ respectively,which was significantly higher than that in tumor adjacent tissues (P ＜0.05 ) ; (2) The expression of p-mTOR was related with p-4EBP1 and p-S6K1 (r =0.458,P ＜ 0.05;r =0.383,P ＜0.05) ; (3) The expression of p-mTOR,p-4EBP1 and p-S6K1 was significantly higher in the patients with lymph node metastasis ( P ＜ 0.05 ),but there was no correlation with other clinicopathological parameters.Conclusion The activation of mTOR signaling pathway plays a certain role in the development of breast carcinoma,and it may promote the process of lymph node metastasis.Meanwhile,as the upstream molecule,mTOR may regulate and control its downstream molecule.