肾癌中Tiam 1的表达及临床意义

目的:探讨T淋巴瘤侵袭转移诱导因子1(Tiam 1)表达与肾癌发生、发展和转移的关系。方法:应用原位杂交及免疫组化方法检测正常肾组织、肾癌石蜡组织标本中Tiam 1mRNA和蛋白的表达情况。用三种不同浓度2μmol/L(T1低浓度)、4μmol/L(T2中浓度)、8μmol/L(T3高浓度)的索坦干扰786-0细胞24h、48h、72h;同时设正常对照组T4(常规培养液)。应用TUNEL法检测各组作用48h细胞凋亡率的变化。应用原位杂交及免疫组化方法检测各组Tiam 1mRNA和蛋白的表达情况。结果:68例肾细胞癌组织中Tiam 1阳性表达率63.2%(43/68),有淋巴结转移组Tiam 1表达率明显高于无淋巴结转移组(P<0.05),TNM分期为Ⅲ～Ⅳ期高于Ⅰ～Ⅱ期,差异有统计学意义(P<0.01);对照组10例正常肾组织中Tiam 1表达均为阴性。Tiam 1基因在786-0细株中表达与肾癌组织中表达相一致。结论:Tiam 1表达与肾癌转移存在密切关系,Tiam 1表达可作为肾癌转移过程中一个有价值的指标;索坦可抑制肾癌细胞的生长,诱导细胞的凋亡,可特异性抑制肾癌786-0细胞中Tiam 1蛋白及mRNA的表达,且具有浓度和时间依赖性。

Expression of Tiam 1 in renal carcinomas and its clinical significance

Objective:To investigate the influence of T lymphoma invasion and metastasis inducing factor 1(Tiam 1)expression on oncogenesis,progression and metastasis in renal carcinomas. Method:Immunohistochemistry and west-blot were used to detect Tiam 1 expression in normal renal epithelium,carcinomas,lymphatic metastasis of renal carcinoma and renal carcinoma cell lines 786-0.After the recovery and the incubation,the 786-0 cells were divided into different groups.:three different concentrations(2,4 and 8 μmol/L)of Sunitinib were used to treat 786-0 cells for 24,48 and 72 h. Result:The positive rate of Tiam 1 expression in renal carcinoma tissue was 63.2%(43/68),Furthermore,the Tiam 1 expression in renal carcinoma with lymph node metastasis was higher than that in renal carcinoma without lymph node metastasis(χ2 = 5.620,P <0.05).which was correlated with clinical stsges(χ2 = 15.308,P<0.01).Normal renal tissue showed negative Tiam 1 stsining.Tiam 1 gene was also highly expressed in 786-0,The results were inconcordance with renal carcinoma tissue. Conclusion:Tiam 1 gene plays an important role in invasion and metastasis of renal carcinoma and is a metastasis-related gene.It may be an useful indicator of the tumor progression and metastasis in renal carcinoma.Sunitinib can specifically inhibit the expressions of Tiam 1 protein and mRNA in the renal cell carcinoma cell line 786-0.and was correlated with different concentrations and time,and can inhibit the cell growth,induce the cell apoptosis.