Document Detail


New mechanism of transforming growth factor-beta signaling in hepatoma: Dramatic up-regulation of tumor initiating cells and epidermal growth factor receptor expression.
MedLine Citation:
PMID:  19261001     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Aim: Transforming growth factor-beta (TGF-beta) has dual activity in tumor cells. We studied the effect of TGF-beta on tumor-initiating cells (TICs), which are similar in self-renewal and differentiation features to normal adult stem cells. Methods: We used side population (SP) cells that exclude DNA binding dye Hoechst 33342 to obtain TICs, studied the differences in the kinetics of the SP cell response to TGF-beta treatment between hepatic tumor cell lines, and performed gene analysis. Results: SP cells from all cell lines have higher proliferative ability compared to non-SP cells and they are drug resistant. TGF-beta treatment increased the percentage of SP cells (%SP) and the survival rate; chemotherapeutic drug resistance developed only in K-251 SP cells. Gene analysis showed that TGF-beta up-regulated epidermal growth factor receptor (EGFR) only in K-251 cells. There were no EGFR mutations in K-251, which had been reported in lung cancer. Knockdown of Smad4 using the small-interfering RNA technique in K-251 cells inhibited EGFR overexpression and significantly decreased the %SP. In contrast, the JNK inhibitor had little effect on EGFR expression or the %SP. Conclusion: TGF-beta treatment of K-251 cells causes tumor progression and the anti-cancer drug resistant phenotype by increasing SP.
Authors:
Takeshi Nishimura; Toshifumi Azuma; Akiko Yokoyama; Hiromi Ochiai; Hidetsugu Saito; Toshifumi Hibi
Publication Detail:
Type:  Journal Article     Date:  2009-02-27
Journal Detail:
Title:  Hepatology research : the official journal of the Japan Society of Hepatology     Volume:  39     ISSN:  1386-6346     ISO Abbreviation:  Hepatol. Res.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9711801     Medline TA:  Hepatol Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  501-9     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, Division of Gastroenterology, Keio University, School of Medicine, Tokyo, Japan.
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