The Role of Estrogen Receptors in Urothelial Cancer

Abstract

Epidemiological data have indicated that there are some sex-related differences in bladder cancer. Indeed, the incidence of bladder cancer in men has been substantially higher than that in women throughout the world, while women tend to have higher stage disease and poorer prognosis. These gender disparities have prompted to investigate sex hormones and their cognitive receptors in bladder cancer. Specifically, estrogen receptors, including estrogen receptor-α and estrogen receptor-β, have been shown to contribute to urothelial carcinogenesis and cancer progression, as well as to modulating chemosensitivity in bladder cancer, although conflicting findings exist. Meanwhile, immunohistochemical studies in surgical specimens have assessed the expression of estrogen receptors and related proteins as well as its associations with clinicopathologic features of bladder cancer and patient outcomes. This review article summarizes and discusses available data indicating that estrogen receptor signaling plays an important role in urothelial cancer.

In Utero Exposure to 3,3′,4,4′, 5-Pentachlorobiphenyl Dose-Dependently Induces N-butyl-4-(hydroxybutyl) Nitrosamine in Rats With Urinary Bladder Carcinoma

“…There are various immunohistochemical studies describing the expression of ERα and ERβ proteins in bladder carcinoma that have produced inconsistent results. 1,14,18 We could not elucidate a mechanism for these conflicting conclusions at the time of our study. Therefore, a further detailed study is necessary.…”

“…[46][47][48][49][50][51] N-butyl-4-(hydroxybutyl) is a procarcinogen and requires metabolic conversion through the α-hydroxylation pathway by CYP1A1 to its ultimate carcinogen metabolite BP-7,8-diol-9,10-epoxide, and binds to DNA and progresses into the initiation-promotion stages of bladder carcinogenesis. 1,52,53 Moreover, several studies have described PCB126 as being anti-estrogenic via crosstalk between the AhR and ERs signaling pathway in human and rodents. 31,[54][55][56] Bladder carcinogenesis has been considered to be enhanced in antiestrogenic situations.…”

Multiple endocrine disorders manifested as gynecomastia in a patient with renal pelvis cancer

“…Available data indicates that estrogen receptor signaling plays an important role in urothelial carcinoma. 19 It has been demonstrated that patients with upper urinary tract (renal pelvis and ureter) UC positive for either estrogen receptor or progesterone receptor had a significantly higher risk of disease‐specific mortality. 20 Recent findings demonstrate that sex hormone receptor signaling plays an important role in the pathogenesis of urothelial carcinoma (revied in 21 ).…”

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

“…Specifically, in a meta-analysis of immunohistochemical studies, AR expression was shown to be rather significantly down-regulated in high-grade or muscle-invasive tumors [ 38 ]. These findings may also raise the possibility of GULP1 modulation by others, such as ER pathways, since significant increases in ERβ expression in high-grade/muscle-invasive bladder cancers have been documented [ 38 , 39 , 40 ].…”