Skip Navigation


Carcinogenesis Advance Access originally published online on August 19, 2008
Carcinogenesis 2008 29(11):2089-2095; doi:10.1093/carcin/bgn198
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
29/11/2089    most recent
bgn198v1
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 arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Leal, J.F.
Right arrow Articles by LLeonart, M.E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leal, J.F.
Right arrow Articles by LLeonart, M.E.
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

S-adenosylhomocysteine hydrolase downregulation contributes to tumorigenesis

J.F. Leal1,{dagger}, I. Ferrer1,{dagger}, C. Blanco-Aparicio1, J. Hernández-Losa2, S. Ramón y Cajal2, A. Carnero1 and M.E. LLeonart2,*

1 Spanish National Cancer Research Center (CNIO), 3 Melchor Fernández Almagro St, Madrid 28029, Spain
2 Pathology Department, Fundació Institut de Recerca Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain

* To whom correspondence should be addressed. Tel: +93 4894169; Fax: +93 4894015; Email: melleona{at}ir.vhebron.net

Correspondence may also be addressed to A.Carnero. Tel: +91 7328000; Fax: +91 2246900; Email: acarnero{at}cnio.es

With the idea to discover novel genes involved in proliferation, we have performed a genome-wide loss-of-function genetic screen to identify additional putative tumor suppressor genes. We have previously identified five genes belonging to different biochemical families. In this report, we focused on the study of one of these genes designated S-adenosylhomocysteine hydrolase (SAHH), which has also been previously identified in an independent short hairpin RNA screening. SAHH inactivation confers resistance to both p53 and p16INK4-induced proliferation arrest. Interestingly, SAHH inactivation inhibits p53 transcriptional activity and impairs DNA damage-induced transcription of p21Cip1. Given that SAHH downregulation modulates senescence in primary cells, we also studied SAHH expression in human tumors at the messenger RNA (mRNA) and protein levels. SAHH mRNA was lost in 50% of tumor tissues from 206 patients with different kinds of tumors in comparison with normal tissue counterparts. Moreover, SAHH protein was also affected in some colon cancers. Such findings may be of relevance to cancer research, suggesting that SAHH might be a largely unexplored tumor suppressor.

Abbreviations: cDNA, complementary DNA; MEFs, mouse embryonic fibroblast; mRNA, messenger RNA; PCR, polymerase chain reaction; RT, reverse transcription; SAHH, S-adenosylhomocysteine hydrolase; shRNA, short hairpin RNA; siRNA, small interpherence RNA

{dagger} These authors contributed equally to this work.

Received March 26, 2008; revised August 12, 2008; accepted August 16, 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.