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dc.contributor.authorHall, Christopher L.en_US
dc.contributor.authorKang, Sonaen_US
dc.contributor.authorMacDougald, Ormond A.en_US
dc.contributor.authorKeller, Evan T.en_US
dc.date.accessioned2007-03-19T17:26:38Z
dc.date.available2007-03-19T17:26:38Z
dc.date.issued2006-03-01en_US
dc.identifier.citationHall, Christopher L.; Kang, Sona; MacDougald, Ormond A.; Keller, Evan T. (2006)."Role of wnts in prostate cancer bone metastases." Journal of Cellular Biochemistry 97(4): 661-672. <http://hdl.handle.net/2027.42/49527>en_US
dc.identifier.issn0730-2312en_US
dc.identifier.issn1097-4644en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/49527
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16447163&dopt=citationen_US
dc.description.abstractProstate cancer (CaP) is unique among all cancers in that when it metastasizes to bone, it typically forms osteoblastic lesions (characterized by increased bone production). CaP cells produce many factors, including Wnts that are implicated in tumor-induced osteoblastic activity. In this prospectus, we describe our research on Wnt and the CaP bone phenotype. Wnts are cysteine-rich glycoproteins that mediate bone development in the embryo and promote bone production in the adult. Wnts have been shown to have autocrine tumor effects, such as enhancing proliferation and protecting against apoptosis. In addition, we have recently identified that CaP-produced Wnts act in a paracrine fashion to induce osteoblastic activity in CaP bone metastases. In addition to Wnts, CaP cells express the soluble Wnt inhibitor dickkopf-1 (DKK-1). It appears that DKK-1 production occurs early in the development of skeletal metastases, which results in masking of osteogenic Wnts, thus favoring osteolysis at the metastatic site. As metastases progress, DKK-1 expression decreases allowing for unmasking of Wnt's osteoblastic activity and ultimately resulting in osteosclerosis at the metastatic site. We believe that DKK-1 is one of the switches that transitions the CaP bone metastasis activity from osteolytic to osteoblastic. Wnt/DKK-1 activity fits a model of CaP-induced bone remodeling occurring in a continuum composed of an osteolytic phase, mediated by receptor activator of NFkB ligand (RANKL), parathyroid hormone-related protein (PTHRP) and DKK-1; a transitional phase, where environmental alterations promote expression of osteoblastic factors (Wnts) and decreases osteolytic factors (i.e., DKK-1); and an osteoblastic phase, in which tumor growth-associated hypoxia results in production of vascular endothelial growth factor and endothelin-1, which have osteoblastic activity. This model suggests that targeting both osteolytic activity and osteoblastic activity will provide efficacy for therapy of CaP bone metastases. J. Cell. Biochem. 97: 661–672, 2006. © 2005 Wiley-Liss, Inc.en_US
dc.format.extent305084 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherLife and Medical Sciencesen_US
dc.subject.otherCell & Developmental Biologyen_US
dc.titleRole of wnts in prostate cancer bone metastasesen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelGeneticsen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Urology, The University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDepartment of Internal Medicine, The University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDepartment of Internal Medicine, The University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDepartment of Urology, The University of Michigan, Ann Arbor, Michigan ; RM 5304 CCGCB, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940.en_US
dc.identifier.pmid16447163en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/49527/1/20735_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/jcb.20735en_US
dc.identifier.sourceJournal of Cellular Biochemistryen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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