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Carcinogenesis Advance Access published online on August 19, 2008
Carcinogenesis, doi:10.1093/carcin/bgn198
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© 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

JF Leal1,#, I Ferrer1,#, C Blanco-Aparicio1, J Hernández-Losa2, Cajal S Ramón y2, A Carnero1,* and ME 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, 08035 Barcelona, Spain

* Corresponding authors

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 shRNA 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 mRNA and protein levels. SAHH mRNA was lost in 50% of tumor tissues from 206 patients with different kinds of tumors in comparison to 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.

# Both authors contributed equially to this work

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


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