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L1-CAM expression in ccRCC correlates with shorter patients survival times and confers chemoresistance in renal cell carcinoma cells

Doberstein, Kai and Wieland, Anja and Lee, Sophia B. Boyoung and Blaheta, Roman A. Alexander and Wedel, Steffen and Moch, Holger and Schraml, Peter and Pfeilschifter, Josef and Kristiansen, Glen and Gutwein, Paul. (2011) L1-CAM expression in ccRCC correlates with shorter patients survival times and confers chemoresistance in renal cell carcinoma cells. Carcinogenesis, Vol. 32, H. 3. pp. 262-270.

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Official URL: http://edoc.unibas.ch/dok/A6007093

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Abstract

Conflicting data exist about the expression of L1 cell adhesion molecule (L1-CAM) in clear cell renal cell carcinoma (ccRCC). To determine the clinical usefulness of L1-CAM as a therapeutic or prognostic marker molecule in renal cancer patients, we analyzed its expression on a cohort of 282 renal cell carcinoma (RCC) patients. L1-CAM expression was found in 49.5% of 282 renal cancer tissues. Importantly, L1-CAM expression in patients with ccRCC was associated with significantly shorter patient survival time. We further present evidence that L1-CAM was involved in the resistance against therapeutic reagents like rapamycin, sunitinib and cisplatin. The downregulation of L1-CAM expression decreased renal cancer cell proliferation and reduced the expression of cyclin D1. In addition, we found out that Von Hippel-Lindau (VHL) deficiency was accompanied by a downregulation of the transcription factor PAX8 and L1-CAM. In normal renal tissue, PAX8 and L1-CAM were co-expressed in collecting duct cells. Importantly, the downregulation of PAX8 by small interfering RNA increased the expression of L1-CAM and concomitantly induced the migration of renal cancer cells. Furthermore, we observed in 65.3% of 282 RCC patients a downregulation of PAX8 expression. With chromatin immunoprecipitation analysis, we additionally demonstrate that PAX8 can bind to the promoter of L1-CAM and we further observed that the downregulation of PAX8 was accompanied by increased L1-CAM expression in a high fraction of ccRCC patients. In summary, we show that VHL and PAX8 are involved in the regulation of L1-CAM in renal cancer and L1-CAM represents an important therapeutic and prognostic marker protein for the treatment of ccRCC.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Schraml, Peter Hans
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0143-3334
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:27 Feb 2014 15:45
Deposited On:27 Feb 2014 15:45

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