Skip Navigation



Carcinogenesis Advance Access published online on December 4, 2008
Carcinogenesis, doi:10.1093/carcin/bgn275
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
30/3/387    most recent
bgn275v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Danilin, S.
Right arrow Articles by Massfelder, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Danilin, S.
Right arrow Articles by Massfelder, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

von Hippel-Lindau tumor suppressor gene-dependent mRNA stabilization of the survival factor parathyroid hormone-related protein in human renal cell carcinoma by the RNA-binding protein HuR

Sabrina Danilin1, Carole Sourbier1, Lionel Thomas1, Sylvie Rothhut1, Véronique Lindner2, Jean-Jacques Helwig1, Didier Jacqmin3, Hervé Lang3 and Thierry Massfelder1,*

1 INSERM U727, Section of Renal Pharmacology and Physiopathology, Strasbourg, 67085 France, University Louis Pasteur, School of Medicine, Strasbourg, 67085 France
2 Hôpitaux Universitaires de Strasbourg, Department of Pathology, Strasbourg-Hautepierre, 67200 France
3 Hôpitaux Universitaires de Strasbourg, Department of Urology, Strasbourg, 67091 France

* To whom correspondence and reprint should be addressed: Tel : 333-90-24-34-56; Fax : 333-90-24-34-59; E-mail: thierry.massfelder{at}medecine.u-strasbg.fr

We have shown that parathyroid hormone-related protein (PTHrP) is a survival factor for human renal cell carcinoma (RCC) and that its expression is negatively regulated by the von Hippel-Lindau (VHL) tumor suppressor gene at the level of mRNA stability, as observed for tumor growth factors (TGFs). Our goals were to analyze the alternative splicing of PTHrP mRNA in human RCC and from these results to identify VHL/HIF (hypoxia-induced factor) system-regulated mRNA binding proteins involved in PTHrP mRNA stability. We used 1) a panel of human RCC cells expressing or not VHL; 2) VHL-deficient 786-0 cells transfected with active or inactive VHL and 3) human RCC samples and corresponding normal tissues. By quantitative real-time RT-PCR analysis the 141 PTHrP mRNA isoform was found to be predominant in all cells and tumors (80%). In cells transfected with VHL, the expression of all isoforms were decreased by 50%. Eight proteins with molecular weights ranging from 20 to 75 kDa were found to bind to biotinylated transcripts spanning the 141 PTHrP mRNA AU-rich 3’-untranslated region whose aboundancy was dependent on VHL expression. The protein having an apparent molecular weight of 30 kDa was identified by Western blot as HuR, a RNA-binding protein with stabilizing functions on various mRNA coding for proteins important in malignant transformation including VEGF and TGF-β. PTHrP expression studies confimed the involvement of HuR in PTHrP up-regulation in this disease. Common mRNA-binding proteins regulated by the VHL/HIF system may constitute new therapeutic opportunities against human RCC that remains refractory to therapies.

Received September 3, 2008; revised November 28, 2008; accepted November 29, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.