title: Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation.
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.
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Young A
authors.initials: YA
authors.lastname: Yoo
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.|The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Meejeon
authors.initials: M
authors.lastname: Roh
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Anum F
authors.initials: AF
authors.lastname: Naseem
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lysy
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37215, USA.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Desouki
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Unno
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.|The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.|Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Sarki A
authors.initials: SA
authors.lastname: Abdulkadir
mesh_terms: D000483:Alleles; D000728:Androgens / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D011467:Prostate / Q000166:cytology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011995:Recombination, Genetic; D012038:Regeneration
chemical_list: D000728:Androgens; C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse