title: Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer.
abstract: BACKGROUND
  The global gene expression profiles of adult and fetal murine prostate stem cells were determined to define common and unique regulators whose misexpression might play a role in the development of prostate cancer.
  
  
  RESULTS
  A distinctive core of transcriptional regulators common to both fetal and adult primitive prostate cells was identified as well as molecules that are exclusive to each population. Elements common to fetal and adult prostate stem cells include expression profiles of Wnt, Shh and other pathways identified in stem cells of other organs, signatures of the aryl-hydrocarbon receptor, and up-regulation of components of the aldehyde dehydrogenase/retinoic acid receptor axis. There is also a significant lipid metabolism signature, marked by overexpression of lipid metabolizing enzymes and the presence of the binding motif for Srebp1. The fetal stem cell population, characterized by more rapid proliferation and self-renewal, expresses regulators of the cell cycle, such as E2f, Nfy, Tead2 and Ap2, at elevated levels, while adult stem cells show a signature in which TGF-beta has a prominent role. Finally, comparison of the signatures of primitive prostate cells with previously described profiles of human prostate tumors identified stem cell molecules and pathways with deregulated expression in prostate tumors including chromatin modifiers and the oncogene, Erg.
  
  
  CONCLUSIONS
  Our data indicate that adult prostate stem or progenitor cells may acquire characteristics of self-renewing primitive fetal prostate cells during oncogenesis and suggest that aberrant activation of components of prostate stem cell pathways may contribute to the development of prostate tumors.
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Roy
authors.initials: R
authors.lastname: Blum
authors.forename: Rashmi
authors.initials: R
authors.lastname: Gupta
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Burger
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ontiveros
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Salm
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Xiong
authors.forename: Alexander
authors.initials: A
authors.lastname: Kamb
authors.forename: Holger
authors.initials: H
authors.lastname: Wesche
authors.forename: Lisa
authors.initials: L
authors.lastname: Marshall
authors.forename: Gene
authors.initials: G
authors.lastname: Cutler
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Wang
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: David
authors.initials: D
authors.lastname: Moscatelli
authors.forename: E Lynette
authors.initials: EL
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D005333:Fetus / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D005810:Multigene Family; D011401:Promoter Regions, Genetic / Q000235:genetics; D011467:Prostate / Q000166:cytology* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D016212:Transforming Growth Factor beta