Abstract:
:Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis. LnCaP, C4-2B, LuCaP23.1, T47D, ZR-75-1, MCF-7, ARCaP and ARCaPM cancer cells that generate osteoblastic, mixed or no bone lesions had the lowest DKK1 expression. The cell lines with negligible expression, LnCaP, C4-2B and T47D, exhibited methylation of the DKK1 promoter. Canonical Wnt signaling activity was then determined and found in all cell lines tested, even in the MDA-MB-231 and PC3 cell lines despite sizeable amounts of DKK1 protein expression expected to block canonical Wnt signaling. A mechanism of DKK1 resistance in the osteolytic cell lines was investigated and determined to be at least partially due to down-regulation of the DKK1 receptors Kremen1 and Kremen2 in the MDA-MB-231 and PC3 cell lines. Combined DKK1 and Kremen expression in cancer cells may serve as predictive markers of the osteoblastic response of breast and prostate cancer bone metastasis.
journal_name
Transl Oncoljournal_title
Translational oncologyauthors
Clines KL,Clines GAdoi
10.1016/j.tranon.2018.04.013subject
Has Abstractpub_date
2018-08-01 00:00:00pages
873-882issue
4issn
1936-5233pii
S1936-5233(17)30434-5journal_volume
11pub_type
杂志文章abstract::Accumulating evidence indicates that CDK2 promotes hyperproliferation and is associated to poor prognosis in multiple cancer cells. However, the physiological role of CDK2 in GBM and the biological mechanism still remains unclear. In this study, we identified that CDK2 expression was significantly enriched in GBM tumo...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.08.007
更新日期:2016-12-01 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC) is a frequent and lethal neoplasia. As recent advances in targeted therapy have not improved ESCC prognosis, characterization of molecular alterations associated to this tumor is of foremost relevance. In this study, we analyze, for the first time, the complete genomic profile...
journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.04.006
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.08.007
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.12181
更新日期:2012-08-01 00:00:00
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journal_title:Translational oncology
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doi:10.1016/j.tranon.2017.10.007
更新日期:2018-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.05.006
更新日期:2019-09-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.10.008
更新日期:2014-12-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13670
更新日期:2013-12-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.11178
更新日期:2011-12-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13844
更新日期:2014-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2015.11.004
更新日期:2015-12-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2020-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.05.001
更新日期:2017-08-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章,评审
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更新日期:2020-09-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.06.005
更新日期:2018-08-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.12322
更新日期:2013-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.11118
更新日期:2011-08-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2020.100812
更新日期:2020-10-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.04.014
更新日期:2014-05-12 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.04.011
更新日期:2019-07-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100931
更新日期:2021-01-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.01.001
更新日期:2020-03-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.09.010
更新日期:2019-01-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.08217
更新日期:2009-03-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.08.010
更新日期:2017-12-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2019.04.022
更新日期:2019-07-01 00:00:00