Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Urology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Anatomy and Cell Biology, School of Medicine and Health Sciences, The George Washington University Cancer Center, The George Washington University, Washington, DC 20052, USA.
Department of Health Informatics, Rutgers School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, NJ 07107, USA; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Stem Cell Reports. 2020 Nov 10;15(5):1026-1036. doi: 10.1016/j.stemcr.2020.10.004.
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.
雄激素受体（AR）在成年前列腺稳态的大多数方面发挥着基本作用，而抗雄激素治疗是前列腺癌治疗的基石。然而，早期的前列腺器官发生发生在青春期前阶段，此时雄激素水平较低，这增加了 AR 功能在前列腺发育过程中受到限制的可能性。在这里，我们使用基因工程小鼠中的诱导型 AR 缺失和谱系追踪，表明基底和腔上皮祖细胞在前列腺发育过程中不需要细胞自主的 AR 活性。我们还证明了存在短暂的双能腔前体细胞，它可以产生腔和基底祖细胞，但也独立于 AR 功能。此外，从发育中的前列腺中分离出的 AR 缺失的腔细胞的分子分析表明它们与野生型细胞相似。我们的研究结果表明，低雄激素水平与前列腺发育过程中的腔可塑性相关，这可能对理解 AR 抑制如何促进前列腺癌中的谱系可塑性具有重要意义。
