DJ-1下调PTEN诱导AR表达促进非激素依赖性乳腺癌转移的研究

DJ-1 inhibits PTEN expression and increases AR in metastasis of non-hormone-dependent breast cancer

目的探讨癌症和帕金森病相关蛋白DJ-1(parkinson disease protein 7,oncogene DJ-1,DJ-1)下调磷酸酯酶与张力蛋白同源物(phosphatase and tensin homolog,PTEN)诱导雄激素受体(androgen receptor,AR)表达促进非激素依赖性乳腺癌转移的机制。方法构建人绿色荧光蛋白表达载体pEGFP/DJ-1;Western blotting对比分析过表达DJ-1基因后MDA-MB-231细胞DJ-1、PTEN、雄激素受体(androgen receptor,AR)的表达;体外迁移与侵袭实验检测过表达DJ-1基因后对MDA-MB-231细胞的迁移与侵袭的影响。收集转移的非激素依赖性乳腺癌和未出现转移的非激素依赖性乳腺癌手术切除标本各40例,采用免疫组织化学检测DJ-1蛋白的表达。结果 Western blotting发现经过转染人DJ-1基因的绿色荧光蛋白表达载体pEGFP/DJ-1后,MDA-MB-231细胞DJ-1的表达水平升高,PTEN的表达水平下降,AR水平升高。体外迁移与侵袭实验发现,转染pEGFP/DJ-1促进SWO-38细胞的迁移和侵袭,与转染空白对照组比较,差异有统计学意义(P<0.05)。发生转移非激素依赖性乳腺癌组织中DJ-1阳性表达率(85.0%)明显高于未发生转移乳腺癌组织(55.0%)(P<0.05)。结论 DJ-1能促进非激素依赖性乳腺癌的迁移与侵袭。这可能与DJ-1抑制PTEN表达,提高AR水平从而促进肿瘤细胞的迁移侵袭能力有关。

[Objective] To investigate the role of DJ-1 down-regulating PTEN expression in metastasis of non-hormone-dependent breast cancer by accumulating AR expression. [Methods] The eukaryotic green fluo- rescent protein vector pEGFP/DJ-1 was constructed and transfected into non-hormone-dependent breast cancer MDA-MB-231 cells. The expression of DJ-1, PTEN and AR were detected by Western blotting. Transwell assay was used to detect 231 cells migration and invasion after transfected pEGFP/DJ-1. The expression of DJ-1 in non-hormone-dependent breast cancer patients with or without metastasis was evaluated by immuno- histochemistry. [Results] After transfection of pEGFP/DJ-1, the expression of DJ-1 and AR were evaluated, but the PTEN expression was decreased. Transwell data showed that pEGFP/DJ-1 promoted MDA-MB-231 cells migration and invasion. And the expression of DJ-1 in non-hormone-dependent breast cancer patients with metastasis （85.0%） was higher than the persons without metastasis （55.0%）. [Conclusion] Over-expres-sion of DJ-1 promotes non-hormone-dependent breast cancer MDA-MB-231 cells migration and invasion through by depressing PTEN expression and activated AR expression.