Different inhibitory effect of imatinib on phosphorylation of mitogen-activated protein kinase and Akt and on proliferation in cells expressing different types of mutant platelet-derived growth factor receptor-alpha

International Journal of Cancer. Journal International Du Cancer
Akiko OhashiSeiichi Hirota

Abstract

Most gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the c-kit gene. Previously, we found 2 types of gain-of-function mutation of the PDGFRA gene, Val561 to Asp and Asp842 to Val, in about half of GISTs without c-kit gene mutations. Although the inhibitory effect of imatinib on various types of activating mutant KIT has been well examined, that on the activating mutant PDGFRA has not been fully investigated. In the present study, we examined the effect of imatinib on autophosphorylation of mutant PDGFRA, phosphorylation of MAPK and of Akt and in vitro cell proliferation using murine Ba/F3 cells stably transfected with one of the 2 murine-type mutated PDGFRA cDNAs. Imatinib almost completely inhibited autophosphorylation of mutant PDGFRA, phosphorylation of MAPK and Akt as well as in vitro cell proliferation at the concentration of 0.01 microM in cells expressing mutant PDGFRA with Val561 to Asp. However, in cells expressing mutant PDGFRA with Asp842 to Val, imatinib almost completely inhibited autophosphorylation of mutant PDGFRA and phosphorylation of MAPK and Akt at 1.0 microM. The concentration contributing to complete inhibition of in vitro cell proliferation was 10 microM. Ba/F3 cells expressing ...Continue Reading

References

Oct 3, 1999·Physiological Reviews·C H Heldin, B Westermark
Mar 7, 2000·The American Journal of Pathology·M L LuxJ A Fletcher
May 12, 2000·Nature Cell Biology·X LiU Eriksson
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
May 2, 2001·Nature Cell Biology·E BergstenU Eriksson
Nov 14, 2001·Lancet·A T van OosteromUNKNOWN European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group
Aug 16, 2002·The New England Journal of Medicine·George D DemetriHeikki Joensuu
Jan 11, 2003·Science·Michael C HeinrichJonathan A Fletcher
Jan 25, 2003·Journal of Gastroenterology and Hepatology·Kazuo KinoshitaYuji Matsuzawa
Apr 3, 2003·International Journal of Cancer. Journal International Du Cancer·Hui ChenSeiichi Hirota
Dec 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael C HeinrichJonathan A Fletcher

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Citations

Nov 17, 2005·Oncogene·Chandra C Kumar, Vincent Madison
Jan 10, 2006·Pathology International·Seiichi Hirota, Koji Isozaki
May 30, 2006·Journal of Clinical Pathology·L Tornillo, L M Terracciano
May 17, 2007·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Sonja E SteigenMarkku Miettinen
Jul 26, 2014·Joint, Bone, Spine : Revue Du Rhumatisme·Gian Luca ErreGiuseppe Passiu
Jun 2, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christopher L CorlessMichael C Heinrich
Jan 30, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Nami Nakagomi, Seiichi Hirota
Nov 15, 2006·Clinical Colorectal Cancer·Chi Tarn, Andrew K Godwin

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