STI571 (Glivec) inhibits the interaction between c-KIT and heat shock protein 90 of the gastrointestinal stromal tumor cell line, GIST-T1
STI571 (Glivec) inhibits the interaction between c-KIT and heat shock protein 90 of the gastrointestinal stromal tumor cell line, GIST-T1
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DOI：
10.1111/j.1349-7006.2005.00018.x
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发表时间：
2005-02-01
期刊：
影响因子：
5.7
通讯作者：
Araki, K
中科院分区：
文献类型：
--
作者：
Nakatani, H;Kobayashi, M;Araki, K
胃肠道间质瘤细胞系GIST-T1的c-kit突变外显子11存在57个碱基对的异质性缺失，GIST-T1细胞中的c-kit蛋白被结构性激活。我们报道了c-kit的特异性抑制剂STI571(Glivec；Novartis，瑞士巴塞尔)可以抑制c-kit在GIST-T1细胞细胞膜上的聚集。此外，STI571还阻止了c-kit和分子伴侣热休克蛋白90(Hsp90)之间的相互作用。Hsp90的抑制剂格尔达那霉素也可以阻止c-kit和Hsp90之间的相互作用，并抑制c-kit的酪氨酸磷酸化。我们的结果表明，c-kit分子聚集在GIST-T1细胞的细胞表面，c-kit与Hsp90之间的相互作用在c-kit激活过程中起重要作用。
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.