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前列腺再生和肿瘤起始过程中管腔祖细胞对雄激素受体的不同需求

Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation.

作者信息

Chua Chee Wai, Epsi Nusrat J, Leung Eva Y, Xuan Shouhong, Lei Ming, Li Bo I, Bergren Sarah K, Hibshoosh Hanina, Mitrofanova Antonina, Shen Michael M

机构信息

Department of Medicine, Columbia University Medical Center, New York, United States.

Department of Genetics and Development, Columbia University Medical Center, New York, United States.

出版信息

Elife. 2018 Jan 15;7:e28768. doi: 10.7554/eLife.28768.

DOI:10.7554/eLife.28768
PMID:29334357
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5807048/
Abstract

Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation . Furthermore, AR loss suppresses tumor formation after deletion of the tumor suppressor in CARNs; however, combined deletion and activation of oncogenic in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer.

摘要

组织特异性的主调控基因在干细胞/祖细胞中起关键作用，且在癌症中通常也很重要。在前列腺中，雄激素受体（AR）是发育和肿瘤发生所必需的主调控因子，但其在前列腺干细胞/祖细胞中的具体功能尚未阐明。我们研究了AR在CARN（去势抵抗性Nkx3.1表达细胞）中的功能，CARN是一种在前列腺再生中起作用的管腔干细胞/祖细胞。利用基因工程小鼠模型和新型前列腺上皮细胞系，我们发现，除了增殖减少外，CARN的祖细胞特性在很大程度上不受AR缺失的影响。此外，AR缺失会抑制CARN中肿瘤抑制因子缺失后的肿瘤形成；然而，在AR缺失的CARN中联合缺失和激活致癌基因会导致具有局灶性神经内分泌分化的肿瘤。我们的研究结果表明，AR调节CARN的特定祖细胞特性，包括其作为前列腺癌起源细胞的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/bbab4be14fa3/elife-28768-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/ad58e1989dfa/elife-28768-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/9587adbb43ab/elife-28768-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/8bec10c2ef48/elife-28768-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/51f4fbffa139/elife-28768-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/75896826847b/elife-28768-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/296ea0972c9e/elife-28768-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/bbab4be14fa3/elife-28768-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/ad58e1989dfa/elife-28768-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/9587adbb43ab/elife-28768-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/8bec10c2ef48/elife-28768-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/51f4fbffa139/elife-28768-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/75896826847b/elife-28768-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/296ea0972c9e/elife-28768-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143d/5807048/bbab4be14fa3/elife-28768-fig6.jpg

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Cell Rep. 2017 Aug 15;20(7):1609-1622. doi: 10.1016/j.celrep.2017.07.061.
2
ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis.ERF突变揭示了控制前列腺癌发生的ETS因子平衡。
Nature. 2017 Jun 29;546(7660):671-675. doi: 10.1038/nature22820. Epub 2017 Jun 14.
3
A computational systems approach identifies synergistic specification genes that facilitate lineage conversion to prostate tissue.
单细胞RNA测序揭示了伴有神经周围浸润的前列腺癌的肿瘤内异质性及恶性进展的潜在机制。
Front Genet. 2023 Jan 9;13:1073232. doi: 10.3389/fgene.2022.1073232. eCollection 2022.
4
Prostate organogenesis.前列腺发生。
Development. 2022 Jun 15;149(12). doi: 10.1242/dev.200394. Epub 2022 Jun 21.
5
Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells.基质 AR 通过抑制分泌腔上皮细胞来抑制前列腺肿瘤的进展。
Cell Rep. 2022 May 24;39(8):110848. doi: 10.1016/j.celrep.2022.110848.
6
Heterogeneity and complexity of the prostate epithelium: New findings from single-cell RNA sequencing studies.前列腺上皮的异质性和复杂性：单细胞 RNA 测序研究的新发现。
Cancer Lett. 2022 Jan 28;525:108-114. doi: 10.1016/j.canlet.2021.10.035. Epub 2021 Oct 30.
7
Prostate cancer cell heterogeneity and plasticity: Insights from studies of genetically-engineered mouse models.前列腺癌细胞异质性和可塑性：遗传工程小鼠模型研究的新见解。
Semin Cancer Biol. 2022 Jul;82:60-67. doi: 10.1016/j.semcancer.2021.06.016. Epub 2021 Jun 18.
8
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