Androgen receptor promotes the migration and invasion of upper urinary tract urothelial carcinoma cells through the upregulation of MMP-9 and COX-2.

ABSTRACT

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.