Division of Urology, Department of Surgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung 427, Taiwan, ROC.
Oncol Rep. 2013 Aug;30(2):979-85. doi: 10.3892/or.2013.2506. Epub 2013 May 28.
Dysregulated androgen receptor (AR) signaling is implicated in several types of tumor, including carcinomas of the prostate, breast, liver and bladder. However, the contribution of AR to the progression of upper urinary tract urothelial carcinomas (UUTUC) has not been fully investigated. In the present study, we demonstrated that the AR is involved in the metastasis and invasiveness of UUTUC cells. We investigated the role of the AR in UUTUC by using UUTUC-derived BFTC 909 cells. The overexpression of AR promotes the migration and invasion of BFTC 909 cells. Expression of migration/invasion-related genes was increased in BFTC 909 cells overexpressing AR determined by qPCR and western blot analyses. The results showed that AR-enhanced migration and invasion of UUTUC cells are linked to the upregulation of the matrix-degrading enzyme MMP-9 and cyclooxygenase (COX)-2. Subsequently, the blocking of MMP-9 and COX-2 signaling by inhibitors suppressed AR-enhanced cell migration and invasion. The results of the present study provide evidence for the first time of the role of AR in the motility and invasion of UUT cancer cells and support the hypothesis that the AR may play a critical role in the establishment of the invasive phenotype in urothelial neoplasia of UUT. Thus, the AR may also serve as a novel biomarker and potential therapeutic target for UUT cancer.
雄激素受体（AR）信号失调与多种肿瘤有关，包括前列腺癌、乳腺癌、肝癌和膀胱癌。然而，AR 对上尿路尿路上皮癌（UUTUC）进展的贡献尚未得到充分研究。在本研究中，我们证明了 AR 参与了 UUTUC 细胞的转移和侵袭。我们通过使用 UUTUC 衍生的 BFTC 909 细胞研究了 AR 在 UUTUC 中的作用。通过 qPCR 和 Western blot 分析，发现 AR 的过表达促进了 BFTC 909 细胞的迁移和侵袭。结果表明，AR 增强 UUTUC 细胞的迁移和侵袭与基质降解酶 MMP-9 和环氧化酶（COX）-2 的上调有关。随后，通过抑制剂阻断 MMP-9 和 COX-2 信号通路抑制了 AR 增强的细胞迁移和侵袭。本研究首次提供了 AR 在 UUT 癌症细胞运动和侵袭中的作用的证据，并支持了 AR 可能在 UUT 上皮性肿瘤的侵袭表型形成中起关键作用的假说。因此，AR 也可能成为 UUT 癌症的新型生物标志物和潜在治疗靶点。
