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Expression of Smad7 in hepatocellular carcinoma and dysplastic nodules: Resistance mechanism to transforming growth factor-β

Authors
 Young Nyun Park  ;  Kwang Jo Chae  ;  Chanil Park  ;  Kyeong Sook Choi  ;  Jinsub Choi  ;  Bong-Kyeong Oh 
Citation
 HEPATO-GASTROENTEROLOGY, Vol.51(56) : 396-400, 2004 
Journal Title
 HEPATO-GASTROENTEROLOGY 
ISSN
 0172-6390 
Issue Date
2004
MeSH
Adult ; Aged ; Carcinoma, Hepatocellular/metabolism* ; DNA-Binding Proteins/metabolism* ; Disease Progression ; Female ; Humans ; Liver Cirrhosis/metabolism ; Liver Neoplasms/metabolism* ; Liver Neoplasms/physiopathology ; Male ; Middle Aged ; Receptors, Transforming Growth Factor beta/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Smad4 Protein ; Smad7 Protein ; Trans-Activators/metabolism* ; Transforming Growth Factor beta/physiology*
Abstract
BACKGROUND/AIMS: Smad7 is an inhibitory Smad of the transforming growth factor (TGF)-beta signaling pathway. To study resistance mechanisms to antiproliferating effect of TGF-beta in human multistep hepatocarcinogenesis, Smad7, Smad4, TGF-beta1 and TGF-beta receptor II were investigated. METHODOLOGY: Smad7 and Smad4 were evaluated in 15 low-grade dysplastic nodules (DNs), 9 high-grade DNs, 6 early hepatocellular carcinomas (eHCCs) and 41 advanced HCCs by immunohistochemistry and in 37 HCCs and corresponding non-HCCs with fresh tissue, the mRNAs of TGF-beta1 and TGF-beta receptor II were analyzed by RT-PCR. RESULTS: Smad7 immunoreactivity in tumor cells was found in 25 (61%) advanced HCCs, in contrast to none of DNs and eHCCs. Smad7 expression was significantly higher in advanced HCCs with increased TGF-beta1 or no decrease of TGF-beta receptor II compared to those of corresponding non-HCCs (p=0.044, p=0.027). Smad4 expression in stellate cells was present in 28 (68%) advanced HCCs, which was higher in smaller sized and better differentiated HCCs. CONCLUSIONS: Smad7, expressed in tumor cells, is considered to be one of resistance mechanisms to increased TGF-beta1 in late stage hepatocarcinogenesis, especially in advanced HCCs without reduced TGF-beta receptor II. Smad4, in stellate cells of HCCs, might be involved in the host resistance to hepatocarcinogenesis.
Full Text
http://www.hepatogastroenterology.org/index.php/withdrawals/item/4365-expression-of-smad7-in-hepatocellular-carcinoma-and-dysplastic-nodules-resistance-mechanism-to-transforming-growth-factor-%25CE%25B2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Park, Chan Il(박찬일)
Choi, Jin Sub(최진섭)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111498
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