scholarly journals Sex Hormone Receptor Signaling in Bladder Cancer: A Potential Target for Enhancing the Efficacy of Conventional Non-Surgical Therapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1169
Author(s):  
Hiroki Ide ◽  
Hiroshi Miyamoto
Keyword(s):  
Bladder Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Surgical Therapy ◽  
Urothelial Cancer ◽  
Hormone Receptors ◽  
Estrogen Receptor Α ◽  
Vital Role ◽  
Sex Hormone ◽  
Sex Steroid Hormone

There have been critical problems in the non-surgical treatment for bladder cancer, especially residence to intravesical pharmacotherapy, including BCG immunotherapy, cisplatin-based chemotherapy, and radiotherapy. Recent preclinical and clinical evidence has suggested a vital role of sex steroid hormone-mediated signaling in the progression of urothelial cancer. Moreover, activation of the androgen receptor and estrogen receptor pathways has been implicated in modulating sensitivity to conventional non-surgical therapy for bladder cancer. This may indicate the possibility of anti-androgenic and anti-estrogenic drugs, apart from their direct anti-tumor activity, to function as sensitizers of such conventional treatment. This article summarizes available data suggesting the involvement of sex hormone receptors, such as androgen receptor, estrogen receptor-α, and estrogen receptor-β, in the progression of urothelial cancer, focusing on their modulation for the efficacy of conventional therapy, and discusses their potential of overcoming therapeutic resistance.

scholarly journals The Role of Steroid Hormone Receptors in Urothelial Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2155
Author(s):  
Hiroki Ide ◽  
Hiroshi Miyamoto
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Glucocorticoid Receptor ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Tumor Development ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Β ◽  
Steroid Hormone Receptors

Preclinical and/or clinical evidence has indicated a potential role of steroid hormone-mediated signaling pathways in the development of various neoplastic diseases, while precise mechanisms for the functions of specific receptors remain poorly understood. Specifically, in urothelial cancer where sex-related differences particularly in its incidence are noted, activation of sex hormone receptors, such as androgen receptor and estrogen receptor-β, has been associated with the induction of tumor development. More recently, glucocorticoid receptor has been implied to function as a suppressor of urothelial tumorigenesis. This article summarizes and discusses available data suggesting that steroid hormone receptors, including androgen receptor, estrogen receptor-α, estrogen receptor-β, glucocorticoid receptor, progesterone receptor and vitamin D receptor, as well as their related signals, contribute to modulating urothelial tumorigenesis.

scholarly journals The Role of Estrogen Receptors in Urothelial Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuro Goto ◽  
Hiroshi Miyamoto
Keyword(s):  
Bladder Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Cancer Progression ◽  
Urothelial Cancer ◽  
Epidemiological Data ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Signaling ◽  
Stage Disease ◽  
Immunohistochemical Studies

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.

Fibromatosis of the Breast

2000 ◽  
Vol 124 (2) ◽  
pp. 276-280 ◽  
Author(s):  
Mojgan Devouassoux-Shisheboran ◽  
David P. Schammel ◽  
Yan-Gao Man ◽  
Fattaneh A. Tavassoli
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Hormone Receptors ◽  
Spindle Cell ◽  
Immunohistochemical Study ◽  
Progesterone Receptors ◽  
Steroid Hormone Receptors ◽  
Childbearing Age ◽  
Sex Steroid Hormone ◽  
Receptor Profile

Abstract Objective.—To predict if antiestrogenic agents are useful in the treatment of breast fibromatoses, we undertook an immunohistochemical study of sex steroid hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) and protein pS2 in 33 cases. Methods.—The morphologic and immunohistochemical findings were correlated to patient menstrual status, which was categorized as childbearing age (n = 15), perimenopausal (n = 8), and postmenopausal (n = 10). Results.—Fibromatoses in women of childbearing age were more cellular, more mitotically active, and displayed a larger proportion of cells with mild atypia than those in perimenopausal and postmenopausal women. The hormonal status of these 3 groups does not explain the morphologic variations observed in these groups, inasmuch as no immunostaining for any of the hormone receptors was detected in the tumors. Conclusions.—The absence of estrogen receptor and pS2 in breast fibromatoses suggests that antiestrogenic agents are unlikely to be beneficial in the management of these tumors. Assessment of the hormone receptor profile is a useful adjunct in the diagnosis of spindle cell lesions of the breast. Although most spindle cell carcinomas as well as fibromatoses of the breast do not express estrogen or progesterone receptors, the absence of androgen receptor reactivity would favor a diagnosis of fibromatosis over that of myofibroblastoma.

scholarly journals Expression of Aromatase, Estrogen Receptor α and β, Androgen Receptor, and Cytochrome P-450scc in the Human Early Prepubertal Testis

2006 ◽  
Vol 60 (6) ◽  
pp. 740-744 ◽  
Author(s):  
Esperanza B Berensztein ◽  
María Sonia Baquedano ◽  
Candela R Gonzalez ◽  
Nora I Saraco ◽  
Jorge Rodriguez ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Estrogen Receptor Α

scholarly journals Differential Expression of Estrogen Receptor-α and -β and Androgen Receptor in the Ovaries of Marmosets and Humans

2000 ◽  
Vol 63 (4) ◽  
pp. 1098-1105 ◽  
Author(s):  
Philippa T.K. Saunders ◽  
Michael R. Millar ◽  
Karin Williams ◽  
Sheila Macpherson ◽  
Diana Harkiss ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Differential Expression ◽  
Estrogen Receptor Α

scholarly journals ATF2 promotes urothelial cancer outgrowth via cooperation with androgen receptor signaling

2018 ◽  
Vol 7 (12) ◽  
pp. 1397-1408 ◽  
Author(s):  
Satoshi Inoue ◽  
Taichi Mizushima ◽  
Hiroki Ide ◽  
Guiyang Jiang ◽  
Takuro Goto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Urothelial Cancer ◽  
Nuclear Translocation ◽  
Significant Inhibition ◽  
Migration And Invasion ◽  
Cycle Phase ◽  
Low Grade ◽  
Urothelial Cells ◽  
Muscle Invasive

We investigated the functional role of ATF2, a transcription factor normally activated via its phosphorylation in response to phospho-ERK/MAPK signals, in the outgrowth of urothelial cancer. In both neoplastic and non-neoplastic urothelial cells, the expression levels of androgen receptor (AR) correlated with those of phospho-ATF2. Dihydrotestosterone treatment in AR-positive bladder cancer cells also induced the expression of phospho-ATF2 and phospho-ERK as well as nuclear translocation and transcriptional activity of ATF2. Meanwhile, ATF2 knockdown via shRNA resulted in significant decreases in cell viability, migration and invasion of AR-positive bladder cancer lines, but not AR-negative lines, as well as significant increases and decreases in apoptosis or G0/G1 cell cycle phase and S or G2/M phase, respectively. Additionally, the growth of AR-positive tumors expressing ATF2-shRNA in xenograft-bearing mice was retarded, compared with that of control tumors. ATF2 knockdown also resulted in significant inhibition of neoplastic transformation induced by a chemical carcinogen 3-methylcholanthrene, as well as the expression of Bcl-2/cyclin-A2/cyclin-D1/JUN/MMP-2, in immortalized human normal urothelial SVHUC cells stably expressing AR, but not AR-negative SVHUC cells. Finally, immunohistochemistry in surgical specimens demonstrated significant elevation of ATF2/phospho-ATF2/phospho-ERK expression in bladder tumors, compared with non-neoplastic urothelial tissues. Multivariate analysis further showed that moderate/strong ATF2 expression and phospho-ATF2 positivity were independent predictors for recurrence of low-grade tumors (hazard ratio (HR) = 2.956, P = 0.045) and cancer-specific mortality of muscle-invasive tumors (HR = 5.317, P = 0.012), respectively. Thus, ATF2 appears to be activated in urothelial cells through the AR pathway and promotes the development and progression of urothelial cancer.

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