Carcinogenesis Advance Access originally published online on June 13, 2006
Carcinogenesis 2007 28(1):21-27; doi:10.1093/carcin/bgl081
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Reduced expression of CYLD in human colon and hepatocellular carcinomas
Department of Internal Medicine I, University Regensburg 93053 Regensburg, Germany
1 Institute of Pathology, University Regensburg 93053 Regensburg, Germany
2 Department of Molecular Medicine, MPI of Biochemistry Martinsried, Germany
*To whom correspondence should be addressed. Tel: +49 941 944 7155; Fax: +49 941 944 7154; Email: claus.hellerbrand{at}klinik.uni-regensburg.de
CYLD was originally identified as a tumor suppressor that is mutated in familial cylindromatosis. Recent studies suggested a role for CYLD in nuclear factor-kappaB (NF-
B) regulation. NF-B activation has been connected with multiple aspects of oncogenesis but the underlying molecular mechanisms of persistent NF-B activation in tumors remain largely unknown. Thus, we evaluated CYLD transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, respectively. CYLD was downregulated or lost in all tumor cell lines investigated as compared with primary human colonic epithelial cells and hepatocytes, respectively. Further, quantitative PCR analysis revealed reduced CYLD mRNA expression in most tumor samples compared with non-tumorous tissue. Analysis on protein level confirmed these findings. Functional assays with CYLD transfected cell lines revealed that CYLD expression decreased NF-B activity. Thus, functional relevant loss of CYLD expression may contribute to tumor development and progression, and may provide a new target for therapeutic strategies.