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Amplification and overexpression of vinculin are associated with increased tumour cell proliferation and progression in advanced prostate cancer

Ruiz, Christian and Holz, David R. and Oeggerli, Martin and Schneider, Sandra and Gonzales, Irma M. and Kiefer, Jeffrey M. and Zellweger, Tobias and Bachmann, Alexander and Koivisto, Pasi A. and Helin, Heikki J. and Mousses, Spyro and Barrett, Michael T. and Azorsa, David O. and Bubendorf, Lukas. (2011) Amplification and overexpression of vinculin are associated with increased tumour cell proliferation and progression in advanced prostate cancer. The journal of pathology, Vol. 223, no. 4. pp. 543-552.

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Official URL: http://edoc.unibas.ch/dok/A6006476

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe > Urologie USB (Bachmann)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe > Urologie USB (Bachmann)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
UniBasel Contributors:Bachmann, Alexander and Bubendorf, Lukas and Zellweger, Tobias
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley
ISSN:0022-3417
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:13 Sep 2013 07:59
Deposited On:13 Sep 2013 07:49

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