Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation

Young A. Yoo, Meejeon Roh, Anum F. Naseem, Barbara Lysy, Mohamed M. Desouki, Kenji Unno and Sarki A. Abdulkadir ()
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Young A. Yoo: Northwestern University Feinberg School of Medicine
Meejeon Roh: Northwestern University Feinberg School of Medicine
Anum F. Naseem: Northwestern University Feinberg School of Medicine
Barbara Lysy: Northwestern University Feinberg School of Medicine
Mohamed M. Desouki: Microbiology and Immunology, Vanderbilt University School of Medicine
Kenji Unno: Northwestern University Feinberg School of Medicine
Sarki A. Abdulkadir: Northwestern University Feinberg School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Identification of defined cell populations with stem/progenitor properties is key for understanding prostate development and tumorigenesis. Here we show that the polycomb repressor protein Bmi1 marks a population of castration-resistant luminal epithelial cells enriched in the mouse proximal prostate. We employ lineage tracing to show that these castration-resistant Bmi1-expressing cells (or CARBs) are capable of tissue regeneration and self-renewal. Notably, CARBs are distinct from the previously described luminal castration-resistant Nkx3.1-expressing cells (CARNs). CARBs can serve as a prostate cancer cell-of-origin upon Pten deletion, yielding luminal prostate tumours. Clonal analysis using the R26R-confetti allele indicates preferential tumour initiation from CARBs localized to the proximal prostate. These studies identify Bmi1 as a marker for a distinct population of castration-resistant luminal epithelial cells enriched in the proximal prostate that can serve as a cell of origin for prostate cancer.

Date: 2016
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DOI: 10.1038/ncomms12943

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