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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2009-11-12
pubmed:abstractText
Recently, we could show that the focal adhesion protein leupaxin (LPXN) is expressed in human prostate carcinomas (PCa) and induces invasiveness of androgen-independent PCa cells. In this study we show that LPXN enhanced the progression of existing PCa in vivo by breeding transgenic mice with prostate-specific LPXN expression and TRAMP mice (transgenic adenocarcinoma of mouse prostate). Double transgenic LPXN/TRAMP mice showed a significant increase in poorly differentiated PCa and distant metastases as compared with control TRAMP mice. Additional studies on primary PCa cells generated from both transgenic backgrounds confirmed the connection regarding LPXN overexpression and increased motility and invasiveness of PCa cells. One mediator of LPXN-induced invasion was found to be the cell-cell adhesion protein p120catenin (p120CTN). Both in vitro and in vivo experiments revealed that p120CTN expression negatively correlates with LPXN expression, followed by a redistribution of beta-catenin. Downregulation of LPXN using small interfering RNAs (siRNAs) resulted in a membranous localization of beta-catenin, whereas strong nuclear accumulation of beta-catenin was observed in p120CTN knockdown cells leading to enhanced transcription of the beta-catenin target gene matrix metalloprotease-7. In conclusion, the present results indicate that LPXN enhances the progression of PCa through downregulation of p120CTN expression and that LPXN could function as a marker for aggressive PCa in the future.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3971-82
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19701244-Adenocarcinoma, pubmed-meshheading:19701244-Animals, pubmed-meshheading:19701244-Blotting, Western, pubmed-meshheading:19701244-Catenins, pubmed-meshheading:19701244-Cell Adhesion Molecules, pubmed-meshheading:19701244-Cell Line, Tumor, pubmed-meshheading:19701244-Cell Movement, pubmed-meshheading:19701244-Disease Progression, pubmed-meshheading:19701244-Down-Regulation, pubmed-meshheading:19701244-Female, pubmed-meshheading:19701244-Gene Knockdown Techniques, pubmed-meshheading:19701244-Humans, pubmed-meshheading:19701244-Male, pubmed-meshheading:19701244-Matrix Metalloproteinase 7, pubmed-meshheading:19701244-Mice, pubmed-meshheading:19701244-Mice, Transgenic, pubmed-meshheading:19701244-Phosphoproteins, pubmed-meshheading:19701244-Prostatic Neoplasms, pubmed-meshheading:19701244-RNA, Small Interfering, pubmed-meshheading:19701244-Transfection, pubmed-meshheading:19701244-beta Catenin
pubmed:year
2009
pubmed:articleTitle
Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression.
pubmed:affiliation
Institute of Human Genetics, University of Göttingen, Göttingen, Niedersachsen 37073, Germany. svoigt1@gwdg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't