1998 Fiscal Year Final Research Report Summary
Role of EGF receptor in the growth, differentiation and apoptosis resistance of gastrointestinal epithelial cells.
| Project/Area Number |
09670546
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
MIYAZAKI Yoshiji Osaka University Medical School, Assistant Professor, 医学部, 助手 (30303960)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Shinya Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
KANAYAMA Shuji Osaka University Medical School, Assistant Professor, 医学部, 助手 (40185913)
SHINOMURA Yasuhisa Osaka University Medical School, Associate Professor, 医学部, 助教授 (90162619)
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| Project Period (FY) |
1997 – 1998
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| Keywords | EGF receptor / EGF-related peptides / HB-EGF / amphiregulin / apoptosis / STAT3 / ras / dominant-negative |
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| Research Abstract |
Gastrointestinal carcinoma cells often overexpress EGF receptor (EGFR) and/or EGF-related peptides including heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR).We investigated the role of the active EGF-related peptide autocrine loop in the growth and apoptosis resistance of gastrointestinal epithelial cells.RGM1 cells and IEC-6 cells are nontransformed rat gastric and intestinal epithelial cell lines, respectively.We demonstrated that these cell lines express HB-EGF and AR, of which transcripts are induced through EGFR- and G-protein-coupled receptor-mediated growth signals.Oncogenic ras induced overexpression of these growth factors resulting in the strong and constitutive tyrosine phosphorylation of EGFR.The apoptosis resistance observed in the oncogenic ras-stimulated cells was dependent on the active EGF-related peptide autocrine loop. We further investigated if the transcription factor STAT3 was involved in the downstream anti-apoptotic signals. We demonstrated that STAT3 is constitutively activated in the ras-stimulated cells depending on the activation of EGFR.We also found that disruption of the STAT3 pathway by introduction of a dominant-negative mutant abolishes the apoptosis resistance of the ras-stimulated cells.Thus, STAT3 appears to be an important mediator of the anti-apoptotic signal in cancerous gastrointestinal epithelial cells which overexpress EGFR and/or EGF-related peptides.
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Research Products
(13 results)
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[Publications] Shusaku Tsutsui, Yasuhisa Shinomura, Shigeki Higashiyama, Yoshifumi Higashimoto, Yoshiji Miyazaki, Shuji Kanayama, Shintaro Hiraoka, Takeshi Minami, Shinji Kitamura, Yoko Murayama, Junichiro Miyagawa, Naoyuki Taniguchi, and Yuji Matsuzawa.: "Induction of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach." Biochem.Biophys.Res.Commun.235(3). 520-523 (1997)
Description
「研究成果報告書概要(欧文)」より
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