Abstract |
The gastrointestinal stromal tumor cell line, GIST-T1, has a heterogenic 57-base pair deletion in exon 11 of the c-kit mutation, and the c-KIT protein in the GIST-T1 cells constitutively activated. We report that STI571 ( Glivec; Novartis, Basel, Switzerland), a specific inhibitor of c-KIT, inhibits the clustering of c-KIT at the cell membrane of the GIST-T1 cells. Furthermore, STI571 prevents the interaction between c-KIT and the molecular chaperone, heat shock protein 90 (Hsp90). Geldanamycin, an inhibitor of Hsp90, also prevents interaction between c-KIT and Hsp90, and inhibits tyrosine phosphorylation of c-KIT. Our results indicate that c-KIT molecules are assembled on the cell surface of the GIST-T1 cells, and that the interaction between c-KIT and Hsp90 plays an important role in c-KIT activation.
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Authors | Hajime Nakatani, Michiya Kobayashi, Toufeng Jin, Takahiro Taguchi, Takeki Sugimoto, Takumi Nakano, Shinichi Hamada, Keijiro Araki |
Journal | Cancer science
(Cancer Sci)
Vol. 96
Issue 2
Pg. 116-9
(Feb 2005)
ISSN: 1347-9032 [Print] England |
PMID | 15723656
(Publication Type: Journal Article)
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Chemical References |
- Benzamides
- Benzoquinones
- HSP90 Heat-Shock Proteins
- Lactams, Macrocyclic
- Piperazines
- Pyrimidines
- Quinones
- Imatinib Mesylate
- Proto-Oncogene Proteins c-kit
- geldanamycin
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Topics |
- Benzamides
- Benzoquinones
- Cell Line, Tumor
- Cell Membrane
(metabolism)
- Cell Survival
(drug effects)
- Drug Interactions
- Gastrointestinal Stromal Tumors
- HSP90 Heat-Shock Proteins
(metabolism)
- Humans
- Imatinib Mesylate
- Lactams, Macrocyclic
- Phosphorylation
- Piperazines
(pharmacology)
- Proto-Oncogene Proteins c-kit
(metabolism)
- Pyrimidines
(pharmacology)
- Quinones
(pharmacology)
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