Objective To discuss the activity of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/AKT pathway and the clinical significance of PTEN protein expression in clear-cell renal-cell carcinoma ( CCRCC) tissues. Methods The protein of PTEN and AKT (phosphorylation at Ser473 ) of 36 paired CCRCC and adjacent non-neoplastic renal samples were analysed by Western-blot. The effect of PTEN on AKT activation was detected by Western-blot after transfected with si-RNA against PTEN in A-498 cell line. Results The significantly increased AKT ( phosphorylation at Ser473 ) with decreased PTEN protein were observed in CCRCC tissues compared with the adjacent non-neoplastic renal samples while the PTEN protein expression had no significant association with pathological parameters. Blocking PTEN resulting in up-regulation of AKT phosphorylation. Conclusions Our findings indicate that as PTEN dominantly inhibits AKT activation, the coexistence of high levels of the PTEN protein with enhanced AKT activation suggests the existence of novel mechanisms which attenuate PTEN function in CCRCC. These mechanisms may reduce PTEN function or increase AKT activation.%目的 探讨人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)/磷脂酰肌醇3-激酶(PI3K)/丝氨酸苏氨酸蛋白激酶(AKT)信号通路在肾透明细胞癌中的活性状况及其与临床特征之间的关系.方法 收集36对肾透明细胞癌及其邻近非肿瘤肾组织,Western blot检测AKT(p-S473)和PTEN蛋白表达,分析两者表达水平的相关性以及PTEN与肿瘤临床特征之间的关系.肾透明细胞癌细胞系A-498转染PTEN si-RNA,观察其对AKT(p-S473)的影响.结果 非肿瘤肾组织中AKT(p-Ser473)为0.945±0.314,PTEN为3.611±0.947.与之比较,肾透明细胞癌中PTEN表达量下降(1.975±0.648),AKT(p-S473)增加(2.751±0.832),差异有统计学意义(P<0.05).PTEN的表达水平与肿瘤临床特征之间无关(P>0.05),细胞系中下调PTEN引起AKT(p-S473)表达升高.结论 肾透明细胞癌中PTEN可以调节PI3K/AKT信号通路的活性,同时PTEN蛋白升高与AKT活性增加同时存在,提示在肾透明细胞癌中还存在使PTEN 功能下降或促进AKT活性增加的因素.
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