@article{88e735e597de4503a7209331bbdcf526,
title = "Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration",
abstract = "The existence of slow-cycling luminal cells in the prostate has been suggested, but their identity and functional properties remain unknown. Using a bigenic mouse model to earmark, isolate, and characterize the quiescent stem-like cells, we identify a label-retaining cell (LRC) population in the luminal cell layer as luminal progenitors. Molecular and biological characterizations show that these luminal LRCs are significantly enriched in the mouse proximal prostate, exhibit relative dormancy, display bipotency in both in vitro and in vivo assays, and express a stem/progenitor gene signature with resemblance to aggressive prostate cancer. Importantly, these LRCs, compared with bulk luminal cells, maintain a lower level of androgen receptor (AR) expression and are less androgen dependent and also castration resistant in vivo. Finally, analysis of phenotypic markers reveals heterogeneity within the luminal progenitor cell pool. Our study establishes luminal LRCs as progenitors that may serve as a cellular origin for castration-resistant prostate cancer. In this article, Tang and colleagues, by using an unbiased bigenic mouse model to specifically earmark, prospectively isolate, and functionally characterize the quiescent stem-like cells, report a label-retaining cell (LRC) population in the mouse prostate luminal cell layer that possesses many stem/progenitor cell activities. These luminal LRCs are developmentally bipotent and intrinsically castration resistant.",
keywords = "cancer stem cells, differentiation, label-retaining cells, luminal progenitors, prostate, prostate cancer, prostate stem cells, quiescence",
author = "Dingxiao Zhang and Collene Jeter and Shuai Gong and Amanda Tracz and Yue Lu and Jianjun Shen and Tang, {Dean G.}",
note = "Funding Information: For the work conducted at the University of Texas MD Anderson Cancer Center (MDACC), we thank the Science Park Animal Core for animal maintenance and care, the Histology Core for IHC studies, P. Whitney for assistance in FACS, Y. Takata for technical help in RNA-seq, and the MDACC Department of Epigenetics and Molecular Carcinogenesis Flow Cytometry and Cell Imaging Core (FCCIC) headed by C.J. For work performed at Roswell Park Cancer Institute (RPCI), we acknowledge the support of several shared resources including flow and image cytometry (K. de Jong) and genomics resources. We thank Dr. J. Kirk for critically reading the manuscript and other Tang lab members for helpful discussions and suggestions. This project was supported by grants from the US NIH ( R01-CA155693 ), Department of Defense ( W81XWH-13-1-0352 , W81XWH-14-1-0575 , and W81XWH-16-1-0575 ), CPRIT ( RP120380 ), and the Chinese Ministry of Science and Technology (MOST) grant 2016YFA0101203 (all to D.G.T.), and by RPCI and NCI center grant P30CA016056 . This study also made use of the Science Park NGS Core, supported by CRPIT Core Facility Support Award RP120348 (to J.S.). We apologize to the colleagues whose work was not cited due to space constraint. Funding Information: For the work conducted at the University of Texas MD Anderson Cancer Center (MDACC), we thank the Science Park Animal Core for animal maintenance and care, the Histology Core for IHC studies, P. Whitney for assistance in FACS, Y. Takata for technical help in RNA-seq, and the MDACC Department of Epigenetics and Molecular Carcinogenesis Flow Cytometry and Cell Imaging Core (FCCIC) headed by C.J. For work performed at Roswell Park Cancer Institute (RPCI), we acknowledge the support of several shared resources including flow and image cytometry (K. de Jong) and genomics resources. We thank Dr. J. Kirk for critically reading the manuscript and other Tang lab members for helpful discussions and suggestions. This project was supported by grants from the US NIH (R01-CA155693), Department of Defense (W81XWH-13-1-0352, W81XWH-14-1-0575, and W81XWH-16-1-0575), CPRIT (RP120380), and the Chinese Ministry of Science and Technology (MOST) grant 2016YFA0101203 (all to D.G.T.), and by RPCI and NCI center grant P30CA016056. This study also made use of the Science Park NGS Core, supported by CRPIT Core Facility Support Award RP120348 (to J.S.). We apologize to the colleagues whose work was not cited due to space constraint. Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2018",
doi = "10.1016/j.stemcr.2017.11.016",
language = "English (US)",
volume = "10",
pages = "228--242",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "1",
}