Fukuchi Minoru, Fukai Yasuyuki, Masuda Norihiro, Miyazaki Tatsuya, Nakajima Masanobu, Sohda Makoto, Manda Ryokuhei, Tsukada Katsuhiko, Kato Hiroyuki, Kuwano Hiroyuki
Department of Surgery I, Gunma University Faculty of Medicine, Maebashi 371-8511, Japan.
Cancer Res. 2002 Dec 15;62(24):7162-5.
Transforming growth factor beta (TGF-beta) regulates growth of various cells, and inactivation of the TGF-beta signaling pathway contributes to tumor progression. Smad2 is phosphorylated and activated by TGF-beta, resulting in the antiproliferative effects of TGF-beta signaling. Smurf2 (Smad ubiquitination regulatory factor 2) was identified as the Smad ubiquitin ligase that induces the ubiquitination and degradation of Smad2. This study was undertaken to elucidate the relationships between Smurf2 expression and the clinicopathological characteristics of patients with esophageal squamous cell carcinoma (SCC) and the correlation between Smurf2 and Smad2 expression. Surgical specimens obtained from 80 patients with esophageal SCC were subjected to immunohistochemical staining. Our data indicated that high-level expression of Smurf2 correlated with depth of invasion, lymph node metastasis, and a poor survival rate. We also found an inverse correlation between the expression of Smurf2 and Smad2. Western blotting analysis of esophageal SCC-derived cell lines revealed similar inverse correlations. We demonstrated that high-level expression of Smurf2 appears to correlate with tumor development and poor prognosis in patients with esophageal SCC and that alteration of Smad2 expression in the TGF-beta signaling pathway may be induced by enhancement of Smad2 degradation mediated by high-level expression of Smurf2.
转化生长因子β（TGF-β）调节多种细胞的生长，TGF-β信号通路的失活促进肿瘤进展。Smad2被TGF-β磷酸化并激活，从而产生TGF-β信号的抗增殖作用。Smurf2（Smad泛素化调节因子2）被鉴定为诱导Smad2泛素化和降解的Smad泛素连接酶。本研究旨在阐明Smurf2表达与食管鳞状细胞癌（SCC）患者临床病理特征之间的关系以及Smurf2与Smad2表达之间的相关性。对80例食管SCC患者的手术标本进行免疫组织化学染色。我们的数据表明，Smurf2的高水平表达与浸润深度、淋巴结转移及低生存率相关。我们还发现Smurf2与Smad2的表达呈负相关。对食管SCC来源的细胞系进行蛋白质印迹分析也显示出类似的负相关。我们证明，Smurf2的高水平表达似乎与食管SCC患者的肿瘤发展和不良预后相关，并且TGF-β信号通路中Smad2表达的改变可能是由Smurf2高水平表达介导的Smad2降解增强所诱导的。
