Expression of estrogen receptors-α and -β in bladder cancer cell lines and human bladder tumor tissue

Abstract

BACKGROUND. Estrogen receptors (ERs) are known to mediate important physiologic responses as well as the growth of some tumors in response to estradiol stimulation. In a previous study the selective ER modulator raloxifene was shown to induce apoptosis in an ERβ-positive bladder cancer cell line. However, the expression of ERβ in human bladder cancer has not been thoroughly investigated. METHODS. ERα and ERβ expression in 224 bladder tumor samples was evaluated using tissue microarray and immunohistochemistry. Levels of ERα and ERβ protein and mRNA expression were determined in several bladder cancer cell lines using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. The effect of estradiol and antiestrogen treatments on RT4 bladder cancer cell growth was determined by cell proliferation assays. RESULTS. Analyses revealed that only 2 human bladder cancers weakly expressed ERα. In contrast, the expression of ERβ was detected in 141 tumors (63%). ERβ was expressed in 58% of WHO Grade 1 and 2 tumors, whereas 70% of Grade 3 tumors demonstrated expression (P=.085). Importantly, although only 53% and 55% of Ta and T1 tumors demonstrated ERβ expression, 80% of T2, 81% of T3, and 75% of T4 tumors showed ERβ expression. The differences in ERβ expression between Ta/T1 and T2/T3/T4 tumors were found to be highly significant (P