| p21CIP-1/WAF-1 induction is required to inhibit prostate cancer growth elicited by deficient expression of the Wnt inhibitor Dickkopf-1. | |
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MedLine Citation:
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PMID: 21098705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Osteoblastic bone metastases are the most common metastases produced by human prostate cancers (PCa). Deregulated activity of Wnt growth factors resulting from overexpression of the Wnt inhibitor Dickkopf-1 (DKK-1) is known to contribute to formation of the osteoblastic component of PCa skeletal bone metastases. In this study, we report that DKK-1 knockdown in osteolytic human PCa cells unexpectedly delays the development of both soft tissue and osseous lesions. PCa cells deficient in DKK-1 expression did not increase canonical Wnt signaling in target osteoblast cell lines; however, DKK-1 knockdown PCa cells exhibited increased expression of the CDK inhibitor p21(CIP1/WAF1) and a 32% increase in G(1) arrest compared with control cells. Ablating p21(CIP1/WAF1) in PCa cells deficient in DKK-1 was sufficient to rescue tumor growth. Collectively, our findings demonstrate that DKK-1 overexpression supports tumor growth in part by restricting expression of p21(CIP1/WAF1) through a mechanism independent of canonical Wnt signaling. |
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Authors:
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Christopher L Hall; Honglai Zhang; Shobun Baile; Mats Ljungman; Stuart Kuhstoss; Evan T Keller |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-23 |
Journal Detail:
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Title: Cancer research Volume: 70 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-08 Completed Date: 2011-02-10 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 9916-26 Citation Subset: IM |
Affiliation:
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Department of Urology, The University of Michigan, Ann Arbor, Michigan, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Bone Neoplasms / genetics, metabolism, secondary Cell Line, Tumor Cyclin-Dependent Kinase Inhibitor p21 / genetics, metabolism* G1 Phase Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Intercellular Signaling Peptides and Proteins / genetics, metabolism* Male Mice Mice, Nude Neoplasms, Experimental / genetics, metabolism*, pathology Oligonucleotide Array Sequence Analysis Prostatic Neoplasms / genetics, metabolism*, pathology RNA Interference Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Transplantation, Heterologous Tumor Burden Wnt Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA093900/CA/NCI NIH HHS; P01 CA093900/CA/NCI NIH HHS; P01 CA093900-06A1/CA/NCI NIH HHS; P01 CA093900-06A18688/CA/NCI NIH HHS; R01 CA071672/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DKK1 protein, human; 0/Intercellular Signaling Peptides and Proteins; 0/Wnt Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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