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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2009

Open Access 01-12-2009 | Research

Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma

Authors: Barbara Seliger, Diana Handke, Elisabeth Schabel, Juergen Bukur, Rudolf Lichtenfels, Reinhard Dammann

Published in: Journal of Translational Medicine | Issue 1/2009

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Abstract

Background

The ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) gene involved in the regulation of cellular ubiquitin levels plays an important role in different cellular processes including cell growth and differentiation. Aberrant expression of UCHL1 has been found in a number of human solid tumors including renal cell carcinoma (RCC). In RCC, UCHL1 overexpression is associated with tumor progression and an altered von Hippel Lindau gene expression.

Methods

To determine the underlying mechanisms for the heterogeneous UCHL1 expression pattern in RCC the UCHL1 promoter DNA methylation status was determined in 17 RCC cell lines as well as in 32 RCC lesions and corresponding tumor adjacent kidney epithelium using combined bisulfite restriction analysis as well as bisulfite DNA sequencing.

Results

UCHL1 expression was found in all 32 tumor adjacent kidney epithelium samples. However, the lack of or reduced UCHL1 mRNA and/or protein expression was detected in 13/32 RCC biopsies and 7/17 RCC cell lines and due to either a total or partial methylation of the UCHL1 promoter DNA. Upon 2'-deoxy-5-azacytidine treatment an induction of UCHL1 mRNA and protein expression was found in 9/17 RCC cell lines, which was linked to the demethylation degree of the UCHL1 promoter DNA.

Conclusion

Promoter hypermethylation represents a mechanism for the silencing of the UCHL1 gene expression in RCC and supports the concept of an epigenetic control for the expression of UCHL1 during disease progression.
Appendix
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Metadata
Title
Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma
Authors
Barbara Seliger
Diana Handke
Elisabeth Schabel
Juergen Bukur
Rudolf Lichtenfels
Reinhard Dammann
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2009
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-7-90

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