膀胱癌中衔接蛋白p66Shc的表达及临床意义

Expression of p66Shc adaptor protein in bladder carcinoma and its clinical significance

目的观察p66Shc蛋白在膀胱癌中的表达,分析其表达与膀胱癌临床分期、病理类型、转移等的关系,以及p66Shc影响膀胱癌细胞增殖、凋亡的分子机制。方法 应用免疫组化法和Western blot技术检测32例膀胱癌中p66Shc蛋白的表达,分析p66Shc蛋白表达和临床病理特征的关系。Western blot技术检测T24细胞中PKCβ和p66Shc蛋白及其磷酸化水平,以及p53、Bax和BCL-2蛋白水平。结果 膀胱癌组织中p66Shc阳性率为65.6%(21/32),其在T3+T4期膀胱癌中的表达显著高于T1+T2期膀胱癌( P <0.05);p66Shc表达与患者年龄、性别、分化程度无关( P >0.05)。LY333531下调T24细胞中PKCβ和p66Shc蛋白及其磷酸化水平,以及下调p53、Bax和上调BCL-2的蛋白水平。结论 p66Shc蛋白在膀胱癌中的表达与膀胱癌临床分期相关,随着pTNM分期增加而表达增多。p66Shc磷酸化促进肿瘤细胞的增殖和凋亡。

Purpose To study the expression of p66Shc in bladder carcinoma and its correlations with clinical stage, pathological type and distant metastasis, and molecular mechanism of p66Shc in bladder cancer cells’ proliferation and apoptosis. Methods Immunohistochemical staining and Western blot were performed to investigate the expression of p66Shc in 32 cases of bladder carcinoma. The was correlations of p66Shc expression with the clinicopathological features were analyzed in the patients. Western blot were performed to detect the protein level of PKCβ, p66Shc, p-PKCβ, p-p66Shc, p53, Bax and BCL-2. Results The expression of p66Shc was highly up-regulated in carcinoma tissues compared with those of adjacent ones. The positive expression rate of p66Shc in 32 cases of bladder carcinoma was 65.6%(21/32), and the expression of p66Shc of T3+T4 patients was significantly higher than that of T1+T2. Western blot showed differential expression of p66Shc, and the difference was statistically significant. LY333531 decreased the expression of PKCβ, p66Shc, p-PKCβ, p-p66Shc, p53, Bax and increased BCL-2 level in T24. Conclusion Adaptor protein p66Shc is highly expressed in bladder carcinoma and associated with a clinical stage of bladder carcinoma. p66Shc phosphorylation may promote the proliferation of cancer cells and apoptosis.