| New mechanism of transforming growth factor-beta signaling in hepatoma: Dramatic up-regulation of tumor initiating cells and epidermal growth factor receptor expression. | |
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MedLine Citation:
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PMID: 19261001 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Takeshi Nishimura; Toshifumi Azuma; Akiko Yokoyama; Hiromi Ochiai; Hidetsugu Saito; Toshifumi Hibi |
Publication Detail:
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Type: Journal Article Date: 2009-02-27 |
Journal Detail:
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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:
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Created Date: 2009-05-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9711801 Medline TA: Hepatol Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 501-9 Citation Subset: - |
Affiliation:
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Department of Internal Medicine, Division of Gastroenterology, Keio University, School of Medicine, Tokyo, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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