Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines

Kazuhiro Noma, Yoshio Naomoto, Mehmet Gunduz, Junji Matsuoka, Tomoki Yamatsuji, Yasuhiro Shirakawa, Tetsuji Nobuhisa, Takaomi Okawa, Munenori Takaoka, Yasuko Tomono, Ohmori Hiroyuki, Esra Gunduz, Noriaki Tanaka

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Mutations of proto-oncogene c-kit in gastrointestinal stromal tumors (GISTs) are considered to cause a constitutive activation of KIT responsible for their oncogenesis. Imatinib has therapeutic potential for GISTs because of its inhibitory effect on KIT kinase activity. However, no study has been published concerning the effects of imatinib on GIST cells with various types of KIT mutation. To investigate the effects of imatinib on various c-kit mutations found in GISTs, cell proliferation and apoptosis assays were performed in two GIST cell lines with different KIT mutations. One of the cell lines, GIST-T1, revealed a heterozygous deletion of exon 11 in the c-kit, while the other cell line, GIST882, possessed a homozygous missense mutation of exon 13 in the c-kit gene. Imatinib inhibited proliferation and induced apoptosis in both cell lines. Imatinib potently suppressed proliferation of the GIST882 cell line at the concentration of 1.0 μM, whereas it inhibited the GIST-T1 at 0.1 μM. In two types of activating mutant KIT, imatinib could inhibit the constitutive activation of both types of KIT mutant, although the antiproliferative effect on GIST882 was weaker than on GIST-T1. Western blot analysis revealed that apoptosis related proteins were activated or suppressed by imatinib in both cell lines in the respective manner. Our results suggest that the apoptotic signal transduction caused by imatinib in GISTs is susceptible to various types of KIT mutation.

Original languageEnglish
Pages (from-to)645-650
Number of pages6
JournalOncology Reports
Volume14
Issue number3
Publication statusPublished - Sep 2005

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Gastrointestinal Stromal Tumors
Stromal Cells
Tumor Cell Line
Mutation
Cell Line
Apoptosis
Exons
Imatinib Mesylate
Proto-Oncogenes
Missense Mutation
Signal Transduction
Carcinogenesis
Phosphotransferases
Western Blotting
Cell Proliferation

Keywords

  • Gastrointestinal tumor
  • KIT-mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines. / Noma, Kazuhiro; Naomoto, Yoshio; Gunduz, Mehmet; Matsuoka, Junji; Yamatsuji, Tomoki; Shirakawa, Yasuhiro; Nobuhisa, Tetsuji; Okawa, Takaomi; Takaoka, Munenori; Tomono, Yasuko; Hiroyuki, Ohmori; Gunduz, Esra; Tanaka, Noriaki.

In: Oncology Reports, Vol. 14, No. 3, 09.2005, p. 645-650.

Research output: Contribution to journalArticle

Noma, K, Naomoto, Y, Gunduz, M, Matsuoka, J, Yamatsuji, T, Shirakawa, Y, Nobuhisa, T, Okawa, T, Takaoka, M, Tomono, Y, Hiroyuki, O, Gunduz, E & Tanaka, N 2005, 'Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines', Oncology Reports, vol. 14, no. 3, pp. 645-650.
Noma, Kazuhiro ; Naomoto, Yoshio ; Gunduz, Mehmet ; Matsuoka, Junji ; Yamatsuji, Tomoki ; Shirakawa, Yasuhiro ; Nobuhisa, Tetsuji ; Okawa, Takaomi ; Takaoka, Munenori ; Tomono, Yasuko ; Hiroyuki, Ohmori ; Gunduz, Esra ; Tanaka, Noriaki. / Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines. In: Oncology Reports. 2005 ; Vol. 14, No. 3. pp. 645-650.
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