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dc.contributor.author
Li, Z. G.
dc.contributor.author
Yang, J.
dc.contributor.author
Vazquez, Elba Susana
dc.contributor.author
Rose, D.
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Vakar Lopez, F.
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Mathew, P.
dc.contributor.author
Lopez, A.
dc.contributor.author
Logothetis, C. J.
dc.contributor.author
Lin, S. H.
dc.contributor.author
Navone, N. M.
dc.date.available
2019-09-18T19:17:13Z
dc.date.issued
2008-01
dc.identifier.citation
Li, Z. G.; Yang, J.; Vazquez, Elba Susana; Rose, D.; Vakar Lopez, F.; et al.; Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone; Nature Publishing Group; Oncogene; 27; 5; 1-2008; 596-603
dc.identifier.issn
0950-9232
dc.identifier.uri
http://hdl.handle.net/11336/83856
dc.description.abstract
The tendency of prostate cancer to produce osteoblastic bone metastases suggests that cancer cells and osteoblasts interact in ways that contribute to cancer progression. To identify factors that mediate these interactions, we compared gene expression patterns between two bone-derived prostate cancer cell lines that produce osteoblastic (MDA PCa 2b) or osteolytic lesions (PC-3). Both cell lines expressed Wnt ligands, including WNT7b, a canonical Wnt implicated in osteogenesis. PC-3 cells expressed 50 times more Dickkopf-1 (DKK1), an inhibitor of Wnt pathways, than did MDA PCa 2b cells. Evaluation of the functional role of these factors (in cocultures of prostate cancer cells with primary mouse osteoblasts (PMOs) or in bone organ cultures) showed that MDA PCa 2b cells activated Wnt canonical signaling in PMOs and that DKK1 blocked osteoblast proliferation and new bone formation induced by MDA PCa 2b cells. MDA PCa 2b cells did not induce bone formation in calvaria from mice lacking the Wnt co-receptor Lrp5. In human specimens, WNT7b was not expressed in normal prostate but was expressed in areas of high-grade prostate intraepithelial neoplasia, in three of nine primary prostate tumor specimens and in 16 of 38 samples of bone metastases from prostate cancer. DKK1 was not expressed in normal or cancerous tissue but was expressed in two of three specimens of osteolytic bone metastases (P=0.0119). We conclude that MDA PCa 2b induces new bone formation through Wnt canonical signaling, that LRP5 mediates this effect, and that DKK1 is involved in the balance between bone formation and resorption that determines lesion phenotype.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Bone Metastases
dc.subject
Dkk1
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Osteoblasts
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Prostate Cancer
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Wnt
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Wnt7b
dc.subject.classification
Otras Ciencias Químicas
dc.subject.classification
Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-02-12T17:07:49Z
dc.journal.volume
27
dc.journal.number
5
dc.journal.pagination
596-603
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Li, Z. G.. University of Texas; Estados Unidos
dc.description.fil
Fil: Yang, J.. University of Texas; Estados Unidos
dc.description.fil
Fil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Rose, D.. University of Texas; Estados Unidos
dc.description.fil
Fil: Vakar Lopez, F.. University of Texas; Estados Unidos
dc.description.fil
Fil: Mathew, P.. University of Texas; Estados Unidos
dc.description.fil
Fil: Lopez, A.. University of Texas; Estados Unidos
dc.description.fil
Fil: Logothetis, C. J.. University of Texas; Estados Unidos
dc.description.fil
Fil: Lin, S. H.. University of Texas; Estados Unidos
dc.description.fil
Fil: Navone, N. M.. University of Texas; Estados Unidos
dc.journal.title
Oncogene
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/sj.onc.1210694
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/1210694
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