Mostrar el registro sencillo del ítem
dc.contributor.author
Wu, Meng
dc.contributor.author
Ingram, Lishann
dc.contributor.author
Tolosa, Ezequiel Julian
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Vera, Renzo Emanuel
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Li, Qianjin
dc.contributor.author
Kim, Sungjin
dc.contributor.author
Ma, Yongjie
dc.contributor.author
Spyropoulos, Demetri D.
dc.contributor.author
Beharry, Zanna
dc.contributor.author
Huang, Jiaoti
dc.contributor.author
Fernandez Zapico, Martin Ernesto
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Cai, Houjian
dc.date.available
2018-10-05T16:49:19Z
dc.date.issued
2016-12
dc.identifier.citation
Wu, Meng; Ingram, Lishann; Tolosa, Ezequiel Julian; Vera, Renzo Emanuel; Li, Qianjin; et al.; Gli transcription factors mediate the oncogenic transformation of prostate basal cells induced by a Kras-androgen receptor axis; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 291; 49; 12-2016; 25749-25760
dc.identifier.issn
0021-9258
dc.identifier.uri
http://hdl.handle.net/11336/61772
dc.description.abstract
Although the differentiation of oncogenically transformed basal progenitor cells is one of the key steps in prostate tumorigenesis, the mechanisms mediating this cellular process are still largely unknown. Here we demonstrate that an expanded p63+ and CK5+ basal/progenitor cell population, induced by the concomitant activation of oncogenic Kras(G12D) and androgen receptor (AR) signaling, underwent cell differentiation in vivo. The differentiation process led to suppression of p63-expressing cells with a decreased number of CK5+ basal cells but an increase of CK8+ luminal tumorigenic cells and revealed a hierarchal lineage pattern consisting of p63+/CK5+ progenitor, CK5+/CK8+ transitional progenitor, and CK8+ differentiated luminal cells. Further analysis of the phenotype showed that Kras-AR axis-induced tumorigenesis was mediated by Gli transcription factors. Combined blocking of the activators of this family of proteins (Gli1 and Gli2) inhibited the proliferation of p63+ and CK5+ basal/progenitor cells and development of tumors. Finally, we identified that Gli1 and Gli2 exhibited different functions in the regulation of p63 expression or proliferation of p63+ cells in Kras-AR driven tumors. Gli2, but not Gli1, transcriptionally regulated the expression levels of p63 and prostate sphere formation. Our study provides evidence of a novel mechanism mediating pathological dysregulation of basal/progenitor cells through the differential activation of the Gli transcription factors. Also, these findings define Gli proteins as new downstream mediators of the Kras-AR axis in prostate carcinogenesis and open a potential therapeutic avenue of targeting prostate cancer progression by inhibiting Gli signaling.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Biochemistry and Molecular Biology
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Gtpase Kras (Kras)
dc.subject
Hedgehog Signaling Pathway
dc.subject
Androgen Receptor
dc.subject
P63
dc.subject
Prostate Cancer
dc.subject.classification
Otras Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Gli transcription factors mediate the oncogenic transformation of prostate basal cells induced by a Kras-androgen receptor axis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-09-19T16:40:25Z
dc.journal.volume
291
dc.journal.number
49
dc.journal.pagination
25749-25760
dc.journal.pais
Estados Unidos
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Wu, Meng. University of Georgia; Grecia
dc.description.fil
Fil: Ingram, Lishann. University of Georgia; Grecia
dc.description.fil
Fil: Tolosa, Ezequiel Julian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Mayo Clinic; Estados Unidos
dc.description.fil
Fil: Vera, Renzo Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Mayo Clinic; Estados Unidos
dc.description.fil
Fil: Li, Qianjin. University of Georgia; Grecia
dc.description.fil
Fil: Kim, Sungjin. University of Georgia; Grecia
dc.description.fil
Fil: Ma, Yongjie. University of Georgia; Grecia
dc.description.fil
Fil: Spyropoulos, Demetri D.. Medical University of South Carolina; Estados Unidos
dc.description.fil
Fil: Beharry, Zanna. Florida Gulf Coast University; Estados Unidos
dc.description.fil
Fil: Huang, Jiaoti. University of Duke; Estados Unidos
dc.description.fil
Fil: Fernandez Zapico, Martin Ernesto. Mayo Clinic; Estados Unidos
dc.description.fil
Fil: Cai, Houjian. University of Georgia; Grecia
dc.journal.title
Journal of Biological Chemistry (online)
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1074/jbc.M116.753129
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/291/49/25749
Archivos asociados