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Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines.
Oncol Rep. 2005 Sep; 14(3):645-50.OR

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 microM, whereas it inhibited the GIST-T1 at 0.1 microM. 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.

Authors+Show Affiliations

Department of Gastroenterological Surgery, Okayama University, 2-5-1 Shikata-cho, Okayamashi 700-8558, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16077968

Citation

Noma, Kazuhiro, et al. "Effects of Imatinib Vary With the Types of KIT-mutation in Gastrointestinal Stromal Tumor Cell Lines." Oncology Reports, vol. 14, no. 3, 2005, pp. 645-50.
Noma K, Naomoto Y, Gunduz M, et al. Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines. Oncol Rep. 2005;14(3):645-50.
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, 14(3), 645-50.
Noma K, et al. Effects of Imatinib Vary With the Types of KIT-mutation in Gastrointestinal Stromal Tumor Cell Lines. Oncol Rep. 2005;14(3):645-50. PubMed PMID: 16077968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines. AU - Noma,Kazuhiro, AU - Naomoto,Yoshio, AU - Gunduz,Mehmet, AU - Matsuoka,Junji, AU - Yamatsuji,Tomoki, AU - Shirakawa,Yasuhiro, AU - Nobuhisa,Tetsuji, AU - Okawa,Takaomi, AU - Takaoka,Munenori, AU - Tomono,Yasuko, AU - Hiroyuki,Ohmori, AU - Gunduz,Esra, AU - Tanaka,Noriaki, PY - 2005/8/4/pubmed PY - 2005/9/16/medline PY - 2005/8/4/entrez SP - 645 EP - 50 JF - Oncology reports JO - Oncol. Rep. VL - 14 IS - 3 N2 - 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 microM, whereas it inhibited the GIST-T1 at 0.1 microM. 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. SN - 1021-335X UR - https://www.unboundmedicine.com/medline/citation/16077968/Effects_of_imatinib_vary_with_the_types_of_KIT_mutation_in_gastrointestinal_stromal_tumor_cell_lines_ L2 - http://www.spandidos-publications.com/or/14/3/645 DB - PRIME DP - Unbound Medicine ER -