UCH-L1在乳腺癌中的表达及其与转移关系的研究

目的研究泛素羧基末端水解酶L1(UCH-L1)与磷酸化p38(p-p38)在乳腺癌组织、细胞系中的表达情况、两种蛋白的表达与临床病理特征的关系以及UCH-L1与乳腺癌侵袭转移的关系。方法用免疫组织化学方法检测乳腺癌组织中UCH-L1与p-p38蛋白的表达情况,用Western Blot方法检测乳腺癌组织以及细胞系中UCH-L1与p-p38蛋白的表达情况。应用UCH-L1特异性抑制剂作用于乳腺癌高侵袭高转移细胞系MDA-MB-435s后,用Western Blot观察UCH-L1与p-p38蛋白表达改变的情况,用Transwell实验检测MDA-MB-435s细胞侵袭潜能的改变。结果 UCH-L1和p-p38蛋白在乳腺浸润性导管癌中的表达高于其在癌旁正常乳腺组织中的表达(P=0.012,P=0.001),二者呈正相关(r=0.397,P=0.000),并与乳腺癌的TNM分期(P=0.017,P=0.010)、淋巴结转移情况(P=0.033,P=0.021)相关。乳腺上皮细胞系MCF-10A、乳腺癌低侵袭低转移细胞系MCF-7和乳腺癌高侵袭高转移细胞系MDA-MB-435s中两种蛋白表达水平呈递增趋势(P均<0.05)。UCH-L1特异性抑制剂可以浓度依赖性地下调MDA-MB-435s细胞系中p-p38蛋白的表达水平(P均<0.05),并能抑制乳腺癌细胞的侵袭转移潜能。结论 UCH-L1、p-p38过表达与乳腺癌的TMN分期、淋巴结转移有关。UCH-L1可能通过上调p-p38介导乳腺癌转移。

Expression of UCH-L1 in breast cancer and its correlation with the metastasis of breast cancer

Objective To investigate the expression of Ubiquitin carboxy terminal hydrolase L1（UCH-L1） protein and Phospho-p38（p-p38） protein in breast cancer tissue and cell lines,and to explore their correlation with clinicopathological characteristics and with metastatic ability of breast cancer. Methods Immunohistochemical method（S-P method） was applied to detect the expression of UCH-L1 and p-p38 proteins in breast cancer tissues,and Western blot was applied to detect their expression in breast cancer tissues and cell lines.We investigated their expression in MDA-MB-435s cells treated with the specific inhibitor of UCH-L1,and the alteration in invasive and migratory potentials was assessed by matrigel invasion assay. Results The expression of UCH-L1 and p-p38 proteins in breast cancer samples was significantly higher than that in normal breast tissue beside the tumor（P=0.012,P=0.001）,while these changes were correlated with clinical TNM staging（P=0.017,P=0.010） and lymphatic metastasis（P=0.033,P=0.021）in breast cancer.The expression of p-p38 and UCH-L1 proteins showed a gradual increase in breast epithelial cell line MCF-10A,breast cancer cell lines MCF-7 and MDA-MB-435s.The decreased UCH-L1 expression resulted in the decreased expression of the p-p38 protein and the decreased invasive and migratory potentials of MDA-MB-435s cells in a dose-dependent manner（P0.05）.Conclusion The over-expression of UCH-L1 and p-p38 is correlated with clinical TNM staging and lymphatic metastasis in breast cancer.UCH-L1 may mediate breast cancer metastasis by up-regulating p-p38.