SASH1-IQGAP1-E-cadherin信号轴可能调节乳腺癌转移  

SASH1-IQGAP1-E-cadherin signal cascade may regulate breast cancer metastasis

作　　者：李述[1] 贺勇[1] 曾兴[2] 陈思蒙[2] 陈礼闻 李璐[2] 李修红[2] 吴娜[2] 唐小淋[2] 曾晓华[4] 周定安[1] 

机构地区：[1]重庆医科大学附属永川医院检验科,重庆402160 [2]重庆医科大学第五临床学院临床医学系,重庆402160 [3]贵州医科大学附属医院肝胆外科,贵州贵阳550001 [4]重庆市肿瘤医院/重庆市肿瘤研究所乳腺疾病诊疗中心,重庆400030

出　　处：《肿瘤》2017年第6期633-641,共9页Tumor

基　　金：重庆市自然科学基金面上项目(编号:cstc2015jcyj A10040)~~

摘　　要：目的:探讨SASH1(SAM-and SH3-domain containing 1)基因作为一个新的抑癌基因,在调节乳腺癌转移过程中的分子作用机制。方法:免疫组织化学法检测人乳腺癌组织中SASH1、含IQ模序的GTP酶活化蛋白1(IQ motif-containing GTPase activating protein 1,IQGAP1)和E-钙黏蛋白(E-cadherin)的表达水平,并分析三者之间的相关性,以及SASH1和IQGAP1表达与乳腺癌患者临床指标的相关性。构建重组质粒HA-IQGAP1-pcDNA3.0和pEGFP-C3-SASH1,并将其转染人胚胎肾细胞HEK-293T,然后采用免疫沉淀-蛋白质印迹法分析SASH1与IQGAP1的相互作用。结果:人乳腺癌组织中,SASH1与IQGAP1的表达存在相关性(P<0.05),而且二者分别与E-cadherin的表达明显相关(P值均<0.001);另外,SASH1和IQGAP1蛋白表达分别与乳腺癌的肿瘤直径和肿瘤分级有相关性(P值均<0.05),但与淋巴结转移无相关性(P值均>0.05)。成功构建重组质粒HA-IQGAP1-pcDNA3.0和pEGFP-C3-SASH1;重组质粒转染HEK-293T细胞后,发现SASH1与IQGAP1之间存在蛋白-蛋白相互作用。结论:SASH1与IQGAP1结合后可发生蛋白-蛋白相互作用,并且与E-cadherin的表达密切相关。推测SASH1可能与IQGAP1和E-cadherin形成一条新的调节乳腺癌转移的信号轴。Objective： To explore the molecular mechanism of SAM-and SH3-domain containing 1 （SASH1） which serves as a novel tumor suppressor gene to regulate breast cancer metastasis.Methods： The expressions of SASH1, IQ motif-containing GTPase activating protein 1 （IQGAP1） and E-cadherin in breast cancer tissues were analyzed by immunohistochemistry （IHC）. The correlation among SASH1, IQGAP1 and E-cadherin, as well as the association of SASH1 and IQGAP1 expressions with the clinical parameters of breast cancer patients were analyzed, respectively. The recombinant plasmids HA-IQGAP1-pcDNA3.0 and pEGFP-C3-SASH1 were cloned and transfected into human embryonic kidney HEK-293T cells. The interaction of SASH1 and IQGAP1 was analyzed by immunoprecipitation-Western blotting.Results： In breast cancer tissues, there was a correlation between the expressions of SASH1 and IQGAP1 （P 〈 0.05）, and the expressions of SASH1 and IQGAP1 proteins were respectively correlated with the expression of E-cadherin （both P 〈 0.001）. In addition, the expressions of SASH1 and IQGAP1 proteins were correlated with tumor diameter and tumor grade （all P 〈 0.05）, but without lymph node metastasis （both P 〉 0.05）. The recombinant plasmids HA-IQGAP1-pcDNA3.0 and pEGFP-C3-SASH1 were constructed successfully. After these recombinant plasmids were transfected into HEK-293T cells, the interaction between SASH1 and IQGAP1 was found.Conclusion： SASH1 interacts with IQGAP1, and which is closely related to the expression of E-cadherin. Therefore, it is suggested that SASH1 may form a new signaling cascade with IQGAP1 and E-cadherin to regulate breast cancer metastasis.

关 键 词：乳腺肿瘤 基因表达调控 钙黏着糖蛋白类 SASH1蛋白 含IQ模序的GTP酶活化蛋白1 

分 类 号：R737.9[医药卫生—肿瘤]