肾透明细胞癌中PTEN/PI3K/AKT信号通路的活性及其临床意义

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.结果 非肿瘤肾组织中AKT(p-Ser473)(0.945±0.314),PTEN(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明显相关(P＞0.05).结论 肾透明细胞癌中PTEN可以调节PDK/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VFEN功能下降或促进AKT活性增加的因素.

The activity and the clinical significance of PTEN/PI3K/AKT signalling pathway in clear-cell renal-cell carcinoma

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 blotting. 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 has no significant association with pathological parameters. Conclusion Our findings indicated 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.