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Bipotent Progenitors Do Not Require Androgen Receptor for Luminal Specification during Prostate Organogenesis
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-11-10 , DOI: 10.1016/j.stemcr.2020.10.004
Maho Shibata 1 , Nusrat J Epsi 2 , Shouhong Xuan 3 , Antonina Mitrofanova 2 , Michael M Shen 3
Affiliation  

Androgen receptor (AR) plays a fundamental role in most aspects of adult prostate homeostasis, and anti-androgen therapy represents the cornerstone of prostate cancer treatment. However, early prostate organogenesis takes place during pre-pubertal stages when androgen levels are low, raising the possibility that AR function is more limited during prostate development. Here, we use inducible AR deletion and lineage tracing in genetically engineered mice to show that basal and luminal epithelial progenitors do not require cell-autonomous AR activity during prostate development. We also demonstrate the existence of a transient bipotent luminal progenitor that can generate luminal and basal progeny, yet is also independent of AR function. Furthermore, molecular analyses of AR-deleted luminal cells isolated from developing prostates indicate their similarity to wild-type cells. Our findings suggest that low androgen levels correlate with luminal plasticity in prostate development and may have implications for understanding how AR inhibition promotes lineage plasticity in prostate cancer.



中文翻译:

双能祖细胞在前列腺器官发生过程中不需要雄激素受体来进行管腔规范

雄激素受体 (AR) 在成人前列腺稳态的大多数方面起着基础性作用,抗雄激素治疗是前列腺癌治疗的基石。然而,早期前列腺器官发生在雄激素水平低的青春期前阶段,这增加了前列腺发育过程中 AR 功能更加有限的可能性。在这里,我们在基因工程小鼠中使用可诱导的 AR 缺失和谱系追踪来表明基底和管腔上皮祖细胞在前列腺发育过程中不需要细胞自主 AR 活动。我们还证明了瞬态双能管腔祖细胞的存在,它可以产生管腔和基底后代,但也独立于 AR 功能。此外,从发育中的前列腺中分离出的 AR 缺失的管腔细胞的分子分析表明它们与野生型细胞的相似性。我们的研究结果表明,低雄激素水平与前列腺发育中的管腔可塑性相关,并且可能对理解 AR 抑制如何促进前列腺癌的谱系可塑性有影响。

更新日期:2020-11-12
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