Sex Hormone Research Center, China Medical University/Hospital, Taichung, 404, Taiwan.
Endocrine. 2013 Feb;43(1):191-9. doi: 10.1007/s12020-012-9762-4. Epub 2012 Aug 1.
Sex hormone receptors, androgen receptor (AR) and estrogen receptors (ERs) including both ERα and ERβ, 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 ERβ immunoreactivities were observed in both UUTUCs, but ERα 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 ERβ 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.
性激素受体,包括雄激素受体(AR)和雌激素受体(ERs),包括 ERα 和 ERβ,介导性激素的作用。在这项研究中,我们旨在评估输尿管和肾盂上尿路上皮癌(UUTUC)中不同肿瘤分期和分级的性激素受体表达及其在肿瘤进展中的可能作用。免疫组织化学用于检测原发性 UUTUC 中 AR 和 ERs 的表达。XTT 活力试验用于评估抗癌药物治疗的细胞反应。划痕愈合试验用于确定细胞迁移能力。AR 和 ERβ 免疫反应性在 UUTUC 中均有观察到,但 ERα 在 UUTUC 中均未检测到。在输尿管标本的 UUTUC 中,发现 AR 表达较高的肿瘤为浅表或低级别肿瘤。相比之下,在输尿管标本的 UUTUC 中,AR 表达在浅表与肌层浸润肿瘤分期或低级别与高级别之间差异较小。此外,在原发性 UUTUC 标本的培养细胞中,功能性 AR 的添加降低了细胞的化学敏感性,但增加了细胞迁移。这些结果提供了第一个在肾盂和输尿管 UUTUC 中显示性激素受体表达模式的数据集。结果表明,输尿管浅表或低级别 UUTUC 中存在更高的 AR 表达呈正相关,并确定了 AR 在 UUTUC 进展中的功能作用。