Source:http://linkedlifedata.com/resource/pubmed/id/16266997
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
21
|
| pubmed:dateCreated |
2005-11-3
|
| pubmed:abstractText |
The ability of Frzb/secreted Frizzled-related protein 3 (sFRP3) to inhibit Wnt signaling and the localization of Frzb/sFRP3 on chromosome 2q to a region frequently deleted in cancers have led some investigators to hypothesize that Frzb/sFRP3 is a tumor suppressor gene. Here, we examined the biological effects of Frzb/sFRP3 on an androgen-independent prostate cancer cell model. We showed that expression of Frzb/sFRP3 in PC-3 cells resulted in decreased colony formation in soft agar and a dramatic inhibition of tumor growth in a xenograft mouse model. When cellular morphology was examined, PC-3 cells expressing Frzb/sFRP3 exhibited an increase in cell-cell contact formation accompanied by a pronounced induction of epithelial markers E-cadherin and keratin-8 and down-regulation of mesenchymal markers N-cadherin, fibronectin, and vimentin. This phenomenon suggested a reversal of epithelial-to-mesenchymal transition and a less invasive phenotype. Indeed, further in vitro studies with a Matrigel assay showed that Frzb/sFRP3 decreased the invasive capacity of PC-3 cells. These changes in the biology of PC-3 cells are associated with a decrease in the expression and activities of both matrix metalloproteinase (MMP)-2 and MMP-9 as well as decreases in AKT activation, cytosolic beta-catenin levels, T-cell factor transcription activity, and expression of Slug and Twist. In addition, transfection of PC-3 with a dominant-negative low-density lipoprotein receptor-related protein 5 (DN-LRP5) coreceptor showed similar biological effects as Frzb/sFRP3 transfection. Together, these data suggest that Frzb/sFRP3 and DN-LRP5 exhibit antitumor activity through the reversal of epithelial-to-mesenchymal transition and inhibition of MMP activities in a subset of prostate cancer.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Keratins,
http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/LRP5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Lrp5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/frizzled related protein-3
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0008-5472
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
65
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
9762-70
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:16266997-Animals,
pubmed-meshheading:16266997-Cadherins,
pubmed-meshheading:16266997-Cattle,
pubmed-meshheading:16266997-Cell Adhesion,
pubmed-meshheading:16266997-Cell Growth Processes,
pubmed-meshheading:16266997-Cell Line, Tumor,
pubmed-meshheading:16266997-Humans,
pubmed-meshheading:16266997-Keratins,
pubmed-meshheading:16266997-LDL-Receptor Related Proteins,
pubmed-meshheading:16266997-Low Density Lipoprotein Receptor-Related Protein-5,
pubmed-meshheading:16266997-Male,
pubmed-meshheading:16266997-Matrix Metalloproteinase 2,
pubmed-meshheading:16266997-Matrix Metalloproteinase 9,
pubmed-meshheading:16266997-Mice,
pubmed-meshheading:16266997-Mice, Nude,
pubmed-meshheading:16266997-Neoplasm Invasiveness,
pubmed-meshheading:16266997-Neoplasms, Hormone-Dependent,
pubmed-meshheading:16266997-Prostatic Neoplasms,
pubmed-meshheading:16266997-Proteins,
pubmed-meshheading:16266997-Signal Transduction,
pubmed-meshheading:16266997-Transfection,
pubmed-meshheading:16266997-Wnt Proteins,
pubmed-meshheading:16266997-Xenograft Model Antitumor Assays,
pubmed-meshheading:16266997-beta Catenin
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Expression of Frzb/secreted Frizzled-related protein 3, a secreted Wnt antagonist, in human androgen-independent prostate cancer PC-3 cells suppresses tumor growth and cellular invasiveness.
|
| pubmed:affiliation |
Department of Urology, University of California, Irvine, Orange, California 92868, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|