Source:http://linkedlifedata.com/resource/pubmed/id/21294127
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
|
pubmed:dateCreated |
2011-2-4
|
pubmed:abstractText |
Androgen withdrawal is the standard treatment for advanced prostate cancer. Although this therapy is initially effective, nearly all prostate cancers become refractory to it. Approximately 15% of these castration-resistant prostate cancers harbour a genomic amplification at 10q22. The aim of this study was to explore the structure of the 10q22 amplicon and to determine the major driving genes. Application of high-resolution array-CGH using the 244k Agilent microarrays to cell lines with 10q22 amplification allowed us to narrow down the common amplified region to a region of 5.8 megabases. We silenced each of the genes of this region by an RNAi screen in the prostate cancer cell lines PC-3 and 22Rv1. We selected genes with a significant growth reduction in the 10q22 amplified cell line PC-3, but not in the non-amplified 22Rv1 cells, as putative target genes of this amplicon. Immunohistochemical analysis of the protein expression of these candidate genes on a tissue microarray enriched for 10q22 amplified prostate cancers revealed vinculin as the most promising target of this amplicon. We found a strong association between vinculin gene amplification and overexpression (p < 0.001). Further analysis of 443 specimens from across all stages of prostate cancer progression showed that vinculin expression was highest in castration-resistant prostate cancers, but negative or very low in benign prostatic hyperplasia (p < 0.0001). Additionally, high tumour cell proliferation measured by Ki67 expression was significantly associated with high vinculin expression in prostate cancer (p < 0.0001). Our data suggest that vinculin is a major driving gene of the 10q22 amplification in prostate cancer and that vinculin overexpression might contribute to prostate cancer progression by enhancing tumour cell proliferation.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
1096-9896
|
pubmed:author |
pubmed-author:AzorsaDavid ODO,
pubmed-author:BachmannAlexanderA,
pubmed-author:BarrettMichael TMT,
pubmed-author:BubendorfLukasL,
pubmed-author:GonzalesIrma MIM,
pubmed-author:HelinHeikki JHJ,
pubmed-author:HolzDavid RDR,
pubmed-author:KieferJeffrey MJM,
pubmed-author:KoivistoPasi APA,
pubmed-author:MoussesSpyroS,
pubmed-author:OeggerliMartinM,
pubmed-author:RuizChristianC,
pubmed-author:SchneiderSandraS,
pubmed-author:ZellwegerTobiasT
|
pubmed:copyrightInfo |
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
|
pubmed:issnType |
Electronic
|
pubmed:volume |
223
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
543-52
|
pubmed:meshHeading |
pubmed-meshheading:21294127-Cell Proliferation,
pubmed-meshheading:21294127-Chromosomes, Human, Pair 10,
pubmed-meshheading:21294127-Comparative Genomic Hybridization,
pubmed-meshheading:21294127-Disease Progression,
pubmed-meshheading:21294127-Gene Amplification,
pubmed-meshheading:21294127-Genetic Association Studies,
pubmed-meshheading:21294127-Humans,
pubmed-meshheading:21294127-Male,
pubmed-meshheading:21294127-Neoplasm Proteins,
pubmed-meshheading:21294127-Polymorphism, Single Nucleotide,
pubmed-meshheading:21294127-Prostatic Hyperplasia,
pubmed-meshheading:21294127-Prostatic Intraepithelial Neoplasia,
pubmed-meshheading:21294127-Prostatic Neoplasms,
pubmed-meshheading:21294127-RNA, Neoplasm,
pubmed-meshheading:21294127-RNA, Small Interfering,
pubmed-meshheading:21294127-Vinculin
|
pubmed:year |
2011
|
pubmed:articleTitle |
Amplification and overexpression of vinculin are associated with increased tumour cell proliferation and progression in advanced prostate cancer.
|
pubmed:affiliation |
Institute for Pathology, University Hospital Basel, Basel, Switzerland. christian.ruiz@unibas.ch
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|