Role of the Androgen Receptor in Gender-Related Cancers

Emilia Sabbatino, Viviana Tutino, F. Licitra, M. Di Donato, G. Castoria, A. Migliaccio, P. Giovannelli
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Abstract

The androgen receptor (AR) is expressed in many cell types, and its related signaling is widely investigated in hormone-dependent cancers such as prostate and breast. The significance of the AR, however, has been detected even in other cancers, including gastric, bladder, kidney, lung, hepatic, and pancreatic, in which growth and spreading are not strictly or notoriously dependent on sex steroid hormone action. The incidence and mortality of these cancers are, however, somewhat related to gender and, specifically, are higher in men than in women, with the ratio reaching 3–4:1 for bladder cancer. This direct correlation between cancer incidence, mortality, and gender makes sex one of the most important risk factors for these cancers and has incited investigation about the role of sex steroid receptors and their activating hormones in gender-related cancers. In these cancers, the AR is often expressed and seems to play a pivotal role in different processes contributing to cancer onset and progression such as growth, spreading, and epithelial to mesenchymal transition (EMT). This manuscript will offer an overview of the role of the AR in many cancers of the respiratory and gastrointestinal systems wherein its role has been at least partially analyzed. Understanding the role of the AR in these tumors could help us to identify a new biomarker for early diagnostic guidance and to develop better therapeutic approaches by directly targeting the AR or its downstream signaling in individual cells of hormone-related cancers at different stages.
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雄激素受体在性别相关癌症中的作用
雄激素受体(AR)在许多细胞类型中表达,其相关信号传导在激素依赖性癌症(如前列腺癌和乳腺癌)中被广泛研究。然而,AR的重要性甚至在其他癌症中也被检测到,包括胃癌、膀胱癌、肾癌、肺癌、肝癌和胰腺癌,在这些癌症中,生长和扩散并不严格或众所周知地依赖于性类固醇激素的作用。然而,这些癌症的发病率和死亡率在一定程度上与性别有关,尤其是男性高于女性,癌症膀胱癌的发病率达到3-4∶1。癌症发病率、死亡率和性别之间的直接相关性使性成为这些癌症最重要的危险因素之一,并促使人们对性类固醇受体及其激活激素在性别相关癌症中的作用进行研究。在这些癌症中,AR经常表达,并且似乎在导致癌症发病和进展的不同过程中发挥关键作用,如生长、扩散和上皮-间质转化(EMT)。本文将概述AR在许多呼吸和胃肠系统癌症中的作用,其中其作用已被至少部分分析。了解AR在这些肿瘤中的作用可以帮助我们确定一种新的生物标志物,用于早期诊断指导,并通过直接靶向不同阶段激素相关癌症个体细胞中的AR或其下游信号,开发更好的治疗方法。
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