Hellerbrand Claus, Bumes Elisabeth, Bataille Frauke, Dietmaier Wolfgang, Massoumi Ramin, Bosserhoff Anja K
Department of Internal Medicine I, University Regensburg, 93053 Regensburg, Germany.
Carcinogenesis. 2007 Jan;28(1):21-7. doi: 10.1093/carcin/bgl081. Epub 2006 Jun 13.
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.
CYLD最初被鉴定为一种在家族性圆柱瘤病中发生突变的肿瘤抑制因子。最近的研究表明CYLD在核因子-κB（NF-κB）调节中发挥作用。NF-κB激活与肿瘤发生的多个方面相关，但肿瘤中持续的NF-κB激活的潜在分子机制仍 largely未知。因此，我们分别评估了CYLD在不同结肠和肝癌细胞系以及组织样本中的转录情况。与原代人结肠上皮细胞和肝细胞相比，在所研究的所有肿瘤细胞系中，CYLD分别下调或缺失。此外，定量PCR分析显示，与非肿瘤组织相比，大多数肿瘤样本中CYLD mRNA表达降低。蛋白质水平分析证实了这些发现。对转染CYLD的细胞系进行的功能测定表明，CYLD表达降低了NF-κB活性。因此，CYLD表达的功能相关缺失可能有助于肿瘤的发生和发展，并可能为治疗策略提供新的靶点。
