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Expression of Smad7 in hepatocellular carcinoma and dysplastic nodules: resistance mechanism to transforming growth factor-beta.

Authors
Park, YN; Chae, KJ; Oh, BK; Choi, J; Choi, KS; Park, C
Citation
Hepato-gastroenterology, 51(56):396-400, 2004
Journal Title
Hepato-gastroenterology
ISSN
0172-6390
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.
MeSH terms
AdultAgedCarcinoma, Hepatocellular/*metabolismDNA-Binding Proteins/*metabolismDisease ProgressionFemaleHumansLiver Cirrhosis/metabolismLiver Neoplasms/*metabolism/physiopathologyMaleMiddle AgedReceptors, Transforming Growth Factor beta/physiologyReverse Transcriptase Polymerase Chain ReactionSignal TransductionSmad4 ProteinSmad7 ProteinTrans-Activators/*metabolismTransforming Growth Factor beta/*physiology
PMID
15086168
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
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