Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer

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dc.contributor.authorBlum, Royen_ZA
dc.contributor.authorGupta, Rashmien_ZA
dc.contributor.authorBurger, Patricia Een_ZA
dc.contributor.authorOntiveros, Christopher Sen_ZA
dc.contributor.authorSalm, Sarah Nen_ZA
dc.contributor.authorXiong, Xiaozhongen_ZA
dc.contributor.authorKamb, Alexanderen_ZA
dc.contributor.authorWesche, Holgeren_ZA
dc.contributor.authorMarshall, Lisaen_ZA
dc.contributor.authorCutler, Geneen_ZA
dc.date.accessioned2015-11-23T12:35:17Z
dc.date.available2015-11-23T12:35:17Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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-β 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/Significance 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.en_ZA
dc.identifier.apacitationBlum, R., Gupta, R., Burger, P. E., Ontiveros, C. S., Salm, S. N., Xiong, X., ... Cutler, G. (2009). Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer. <i>PLoS One</i>, http://hdl.handle.net/11427/15321en_ZA
dc.identifier.chicagocitationBlum, Roy, Rashmi Gupta, Patricia E Burger, Christopher S Ontiveros, Sarah N Salm, Xiaozhong Xiong, Alexander Kamb, Holger Wesche, Lisa Marshall, and Gene Cutler "Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/15321en_ZA
dc.identifier.citationBlum, R., Gupta, R., Burger, P. E., Ontiveros, C. S., Salm, S. N., Xiong, X., ... & Wilson, E. L. (2008). Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer. PloS one, 4(5), e5722. doi:10.1371/journal.pone.0005722en_ZA
dc.identifier.ris TY - Journal Article AU - Blum, Roy AU - Gupta, Rashmi AU - Burger, Patricia E AU - Ontiveros, Christopher S AU - Salm, Sarah N AU - Xiong, Xiaozhong AU - Kamb, Alexander AU - Wesche, Holger AU - Marshall, Lisa AU - Cutler, Gene AB - 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. METHODOLOGY/PRINCIPAL FINDINGS: 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-β 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/Significance 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. DA - 2009 DB - OpenUCT DO - 10.1371/journal.pone.0005722 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer TI - Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer UR - http://hdl.handle.net/11427/15321 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15321
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0005722
dc.identifier.vancouvercitationBlum R, Gupta R, Burger PE, Ontiveros CS, Salm SN, Xiong X, et al. Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer. PLoS One. 2009; http://hdl.handle.net/11427/15321.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 Blum et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherProstate glanden_ZA
dc.subject.otherProstate canceren_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherTGF-beta signaling cascadeen_ZA
dc.subject.otherGene regulationen_ZA
dc.subject.otherLipid metabolismen_ZA
dc.subject.otherStem cellsen_ZA
dc.subject.otherAdultsen_ZA
dc.titleMolecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate canceren_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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