title: STI571 (Glivec) inhibits the interaction between c-KIT and heat shock protein 90 of the gastrointestinal stromal tumor cell line, GIST-T1.
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.
authors.affiliation: Department of Tumor Surgery, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan. nakatanh@kochi-ms.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakatani
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toufeng
authors.initials: T
authors.lastname: Jin
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taguchi
authors.forename: Takeki
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Nakano
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hamada
authors.forename: Keijiro
authors.initials: K
authors.lastname: Araki
mesh_terms: D001549:Benzamides; D016227:Benzoquinones; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D046152:Gastrointestinal Stromal Tumors; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D047029:Lactams, Macrocyclic; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology
chemical_list: D001549:Benzamides; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D010879:Piperazines; D011743:Pyrimidines; D011809:Quinones; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; C001277:geldanamycin
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