Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases
dc.contributor.author | Bu, Guojun | en_US |
dc.contributor.author | Lu, Wenyan | en_US |
dc.contributor.author | Liu, Chia-Chen | en_US |
dc.contributor.author | Selander, Katri | en_US |
dc.contributor.author | Yoneda, Toshiyuki | en_US |
dc.contributor.author | Hall, Christopher L. | en_US |
dc.contributor.author | Keller, Evan T. | en_US |
dc.contributor.author | Li, Yonghe | en_US |
dc.date.accessioned | 2008-07-01T14:07:17Z | |
dc.date.available | 2009-09-02T14:40:29Z | en_US |
dc.date.issued | 2008-09-01 | en_US |
dc.identifier.citation | Bu, Guojun; Lu, Wenyan; Liu, Chia-Chen; Selander, Katri; Yoneda, Toshiyuki; Hall, Christopher; Keller, Evan T.; Li, Yonghe (2008). "Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases." International Journal of Cancer 123(5): 1034-1042. <http://hdl.handle.net/2027.42/60217> | en_US |
dc.identifier.issn | 0020-7136 | en_US |
dc.identifier.issn | 1097-0215 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/60217 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18546262&dopt=citation | en_US |
dc.description.abstract | Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/Β-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/Β-catenin antagonist. In the present study, we demonstrated that activation of Wnt/Β-catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/Β-catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell-produced Dkk1 blocked Wnt3A-induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti-Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A-induced NF-kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A-induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer-produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 508372 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 | Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Urology, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Urology, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationother | Department of Pediatrics, Washington University School of Medicine, St. Louis, MO | en_US |
dc.contributor.affiliationother | Departments of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL | en_US |
dc.contributor.affiliationother | Department of Pediatrics, Washington University School of Medicine, St. Louis, MO | en_US |
dc.contributor.affiliationother | Department of Medicine, University of Alabama at Birmingham, Birmingham, AL | en_US |
dc.contributor.affiliationother | Endocrine Research, Department of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX | en_US |
dc.contributor.affiliationother | Departments of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL ; Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35255-5305 | en_US |
dc.identifier.pmid | 18546262 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/60217/1/23625_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/ijc.23625 | en_US |
dc.identifier.source | International Journal of Cancer | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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