Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis
dc.contributor.author | Hall, Christopher L. | en_US |
dc.contributor.author | Daignault, Stephanie D. | en_US |
dc.contributor.author | Shah, Rajal B. | en_US |
dc.contributor.author | Pienta, Kenneth J. | en_US |
dc.contributor.author | Keller, Evan T. | en_US |
dc.date.accessioned | 2008-08-27T20:04:12Z | |
dc.date.available | 2009-11-06T18:12:56Z | en_US |
dc.date.issued | 2008-09-15 | en_US |
dc.identifier.citation | Hall, Christopher L.; Daignault, Stephanie D.; Shah, Rajal B.; Pienta, Kenneth J.; Keller, Evan T. (2008). "Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis." The Prostate 68(13): 1396-1404. <http://hdl.handle.net/2027.42/60894> | en_US |
dc.identifier.issn | 0270-4137 | en_US |
dc.identifier.issn | 1097-0045 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/60894 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18561248&dopt=citation | en_US |
dc.description.abstract | BACKGROUND Prostate cancer (PCa) frequently metastasizes to the bone and induces osteoblastic lesions. We previously demonstrated through over-expression of the Wnt inhibitor dickkopf-1 (DKK-1) that Wnts contribute to the osteoblastic component of PCa osseous lesions in vivo. METHODS To test the clinical significance of DKK-1 expression during PCa progression, tissue microarrays were stained for DKK-1 protein by immunohistochemistry. RESULTS DKK-1 expression index (EI) was found to increase in PIN and primary lesions compared to non-neoplastic tissue (106 ± 10 vs. 19 ± 6, respectively, where the EI is the product of the percent expression and staining intensity). DKK-1 expression was also found to be higher in all PCa metastatic lesions (56 ± 21 EI) compared to non-neoplastic tissues but was significantly decreased versus primary PCa lesions ( P < 0.008). The decline in DKK-1 correlated with a shift of Β-catenin staining from the nucleus to the cytoplasm suggesting possible mechanism for the observed decrease in DKK-1 levels during PCa progression. Within metastatic lesions, DKK-1 expression was least abundant in PCa bone metastases relative to all soft tissue PCa metastatic lesions except lymph node metastases. High DKK-1 expression within PCa metastases was further associated with shorter over-all patient survival. CONCLUSIONS Taken together, these data demonstrate that elevated DKK-1 expression is an early event in PCa and that as PCa progresses DKK-1 expression declines, particularly in advanced bone metastases. The decline of DKK-1 in bone metastases can unmask Wnts' osteoblastic activity. These data support a model in which DKK-1 is a molecular switch that transitions the phenotype of PCa osseous lesions from osteolytic to osteoblastic. Prostate 68: 1396–1404, 2008. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 321237 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Urology, The University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Urology, The University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pathology, The University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Urology, The University of Michigan, Ann Arbor, Michigan ; RM 5308 CCGCB, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940. | en_US |
dc.identifier.pmid | 18561248 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/60894/1/20805_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/pros.20805 | en_US |
dc.identifier.source | The Prostate | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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