Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Fukuchi M,Fukai Y,Masuda N,Miyazaki T,Nakajima M,Sohda M,Manda R,Tsukada K,Kato H,Kuwano Hsubject
Has Abstractpub_date
2002-12-15 00:00:00pages
7162-5issue
24eissn
0008-5472issn
1538-7445journal_volume
62pub_type
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