Depletion of androgen receptor low molecular weight isoform reduces bladder tumor cell viability and induces apoptosis

Katleba, Kimberley D.; Lombard, Alan P.; Tsamouri, Maria Malvina; Baek, Han Bit; Nishida, Kristine; Libertini, Stephen J.; Platero, Alexander J.; Hong, Ai; Pan, Chong Xian; Ghosh, Paramita M.; Mudryj, Maria

doi:10.1016/j.canlet.2021.01.029

Cited by 7 publications

(14 citation statements)

References 38 publications

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“…Once in the nucleus, these variants can activate transcription to promote the proliferation. These variants have been identified in bladder cancer [67].…”

Section: Ar Signaling In Bladder Cancer Carcinogenesis: Initiation and Promotionmentioning

confidence: 99%

“…Yang et al, 2020 have reported the differential effects of the AR in the promotion of cancer metastasis in bladder cancer, while suppressing prostate cancer metastasis [117]. Yasui et al, 2019 also found that a high AR mRNA-expressing group tended to have a longer recurrence-free survival, and Katleba et al, 2021 found a low molecular weight variant of the androgen receptor in most bladder cancer malignancies, missing the ligand binding domain [67,118].…”

Section: Bladder Cancer Therapiesmentioning

confidence: 99%

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The Role of Androgens and Androgen Receptor in Human Bladder Cancer

et al. 2021

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Bladder cancer (urothelial carcinoma) is one of the most frequently diagnosed neoplasms, with an estimated half a million new cases and 200,000 deaths per year worldwide. This pathology mainly affects men. Men have a higher risk (4:1) of developing bladder cancer than women. Cigarette smoking and exposure to chemicals such as aromatic amines, and aniline dyes have been established as risk factors for bladder cancer and may contribute to the sex disparity. Male internal genitalia, including the urothelium and prostate, are derived from urothelial sinus endoderm; both tissues express the androgen receptor (AR). Several investigations have shown evidence that the AR plays an important role in the initiation and development of different types of cancer including bladder cancer. In this article, we summarize the available data that help to explain the role of the AR in the development and progression of bladder cancer, as well as the therapies used for its treatment.

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“…Once in the nucleus, these variants can activate transcription to promote the proliferation. These variants have been identified in bladder cancer [67].…”

Section: Ar Signaling In Bladder Cancer Carcinogenesis: Initiation and Promotionmentioning

confidence: 99%

Section: Bladder Cancer Therapiesmentioning

confidence: 99%

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

et al. 2021

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“…Meanwhile, eventual resistance to standard hormonal therapy remains a critical issue in patients with prostate or breast cancer. Indeed, an AR variant, which is implicated in the development of castration-resistant prostate cancer, has recently been identified in bladder cancer [ 89 ]. Further investigation of AR and ERs, as well as other molecules directly or indirectly regulated by AR/ER signals, is required for determining the precise actions of androgens/estrogens in bladder cancer cells, in relation to their impact on modulating sensitivity to conventional therapy, as well as underlying molecular mechanisms for their actions.…”

Section: Discussionmentioning

confidence: 99%

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

Ide

Miyamoto

2021

Cells

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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.

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“…There also appear to be some demographic genetic differences-for example, more female dogs suffer from BlCa compared to male dogs-whereas in human patients it is the other way around. This may be related to the fact that most male dogs are castrated at a fairly young age and therefore would not respond to hormones as human patients would, perhaps providing a protective effect [39]. Therefore, dog patients will not follow hormone dependent aspects of human MIUC such as those recently reported on [39].…”

Section: Differences Between Canine and Human Miucmentioning

confidence: 98%

“…This may be related to the fact that most male dogs are castrated at a fairly young age and therefore would not respond to hormones as human patients would, perhaps providing a protective effect [39]. Therefore, dog patients will not follow hormone dependent aspects of human MIUC such as those recently reported on [39]. Despite these differences, there are several similarities in the signaling pathways that lead to MIUC development in both canine and human patients that make the use of canines in preclinical trials for MIUC more promising.…”

Section: Differences Between Canine and Human Miucmentioning

confidence: 99%

Comparative Cancer Cell Signaling in Muscle-Invasive Urothelial Carcinoma of the Bladder in Dogs and Humans

et al. 2021

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Muscle-invasive urothelial carcinoma (MIUC) is the most common type of bladder malignancy in humans, but also in dogs that represent a naturally occurring model for this disease. Dogs are immunocompetent animals that share risk factors, pathophysiological features, clinical signs and response to chemotherapeutics with human cancer patients. This review summarizes the fundamental pathways for canine MIUC initiation, progression, and metastasis, emerging therapeutic targets and mechanisms of drug resistance, and proposes new opportunities for potential prognostic and diagnostic biomarkers and therapeutics. Identifying similarities and differences between cancer signaling in dogs and humans is of utmost importance for the efficient translation of in vitro research to successful clinical trials for both species.

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Depletion of androgen receptor low molecular weight isoform reduces bladder tumor cell viability and induces apoptosis

Cited by 7 publications

References 38 publications

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

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

Comparative Cancer Cell Signaling in Muscle-Invasive Urothelial Carcinoma of the Bladder in Dogs and Humans

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