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

  • Authors:
    • 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
  • View Affiliations

  • Published online on: September 1, 2005     https://doi.org/10.3892/or.14.3.645
  • Pages: 645-650
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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 trans-duction caused by imatinib in GISTs is susceptible to various types of KIT mutation.

Related Articles

Journal Cover

September 2005
Volume 14 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Noma K, Naomoto Y, Gunduz M, Matsuoka J, Yamatsuji T, Shirakawa Y, Nobuhisa T, Okawa T, Takaoka M, Tomono Y, Tomono Y, et al: Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines. Oncol Rep 14: 645-650, 2005
APA
Noma, K., Naomoto, Y., Gunduz, M., Matsuoka, J., Yamatsuji, T., Shirakawa, Y. ... Tanaka, N. (2005). Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines. Oncology Reports, 14, 645-650. https://doi.org/10.3892/or.14.3.645
MLA
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."Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines". Oncology Reports 14.3 (2005): 645-650.
Chicago
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."Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines". Oncology Reports 14, no. 3 (2005): 645-650. https://doi.org/10.3892/or.14.3.645