Reduced expression of CYLD in human colon and hepatocellular carcinomas.
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-kappaB) regulation. NF-kappaB activation has been connected with multiple aspects of oncogenesis but the underlying molecular mechanisms of persistent NF-kappaB 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-kappaB activity. Thus, functional relevant loss of CYLD expression may contribute to tumor development and progression, and may provide a new target for therapeutic strategies.
Hellerbrand
Claus
C
Department of Internal Medicine I, University Regensburg, 93053 Regensburg, Germany. claus.hellerbrand@klinik.uni-regensburg.de
Bumes
Elisabeth
E
Bataille
Frauke
F
Dietmaier
Wolfgang
W
Massoumi
Ramin
R
Bosserhoff
Anja K
AK
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000074749:Deubiquitinating Enzyme CYLD; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD