The expression and actions of androgen receptor in upper urinary tract urothelial carcinoma (UUTUC) tissues and the primary cultured cells

Sex hormone receptors, androgen receptor (AR) and estrogen receptors (ERs) including both ER alpha and ER beta, mediate the actions of sex hormones. In this study, we aimed to evaluate sex hormone receptors expression in upper urinary tract urothelial carcinomas (UUTUCs) of ureter and renal pelvis with different tumor stages and grades as well as their possible roles in tumor progression. Immunohistochemistry was used to assay the expression of AR and ERs in the primary UUTUCs. XTT viability test was applied to evaluate cell responses for anticancer drug treatment. Wound healing assay was performed to determine cell migration abilities. AR and ER beta immunoreactivities were observed in both UUTUCs, but ER alpha was not detected in either UUTUCs. In UUTUC of ureter specimens, higher AR expression was found in superficial or lower grade tumors. In contrast, little difference of ER beta expression was found in superficial versus muscle-invasive tumor stages or low grades versus high grades in UUTUCs of ureter specimens. Furthermore in the primary cultured cells from UUTUC specimens, the addition of functional AR reduced cell chemosensitivity, but increased cell migration. These results provide the first data showing the expression patterns of sex hormone receptors in both renal pelvis and ureter UUTUCs. From results, we concluded that there is a positive correlation for higher AR expression found in superficial or low-grade UUTUCs of ureter and identified the functional roles of AR in UUTUC progression.