Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS:
Synovial sarcoma cell lines expressed multiple FGF genes especially those expressed in neural tissues, among which FGF8 showed growth stimulatory effects in all synovial sarcoma cell lines. FGF signals in synovial sarcoma induced the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38MAPK but not c-Jun NH2-terminal kinase. Disruption of the FGF signaling pathway in synovial sarcoma by specific inhibitors of FGFR caused cell cycle arrest leading to significant growth inhibition both in vitro and in vivo. Growth inhibition by the FGFR inhibitor was associated with a down-regulation of phosphorylated ERK1/2 but not p38MAPK, and an ERK kinase inhibitor also showed growth inhibitory effects for synovial sarcoma, indicating that the growth stimulatory effect of FGF was transmitted through the ERK1/2. CONCLUSIONS:
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Authors | Tatsuya Ishibe, Tomitaka Nakayama, Takeshi Okamoto, Tomoki Aoyama, Koichi Nishijo, Kotaro Roberts Shibata, Yasuko Shima, Satoshi Nagayama, Toyomasa Katagiri, Yusuke Nakamura, Takashi Nakamura, Junya Toguchida |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 11
Issue 7
Pg. 2702-12
(Apr 01 2005)
ISSN: 1078-0432 [Print] United States |
PMID | 15814652
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Protein Isoforms
- Pyrimidines
- Pyrroles
- RNA, Messenger
- Receptors, Fibroblast Growth Factor
- Recombinant Proteins
- SU 5402
- Fibroblast Growth Factors
- Urea
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Mitogen-Activated Protein Kinases
- PD 166866
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Topics |
- Animals
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Dose-Response Relationship, Drug
- Enzyme Activation
(drug effects)
- Female
- Fibroblast Growth Factors
(genetics, metabolism, pharmacology)
- Gene Expression Regulation, Neoplastic
- Humans
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Mitogen-Activated Protein Kinases
(metabolism)
- Phosphorylation
(drug effects)
- Protein Isoforms
(genetics)
- Pyrimidines
(pharmacology)
- Pyrroles
(pharmacology)
- RNA, Messenger
(genetics, metabolism)
- Receptors, Fibroblast Growth Factor
(antagonists & inhibitors, genetics)
- Recombinant Proteins
(pharmacology)
- Reverse Transcriptase Polymerase Chain Reaction
- Sarcoma, Synovial
(genetics, pathology, prevention & control)
- Signal Transduction
(drug effects, physiology)
- Urea
(analogs & derivatives, pharmacology)
- Xenograft Model Antitumor Assays
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