AIM: To estimate whether STI571 inhibits the expression of vascular endothelial growth factor (VEGF) in the gastrointestinal stromal tumor (GIST) cells. METHODS: We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor (SCF). Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by MTT assay. RESULTS: Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by STI571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by MTT assay. CONCLUSION: Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by STI571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.
AIM: To estimate whether STI571 inhibits the expression of vascular endothelial growth factor (VEGF) in the gastrointestinal stromal tumor (GIST) cells. METHODS: We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor (SCF). Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by MTT assay. RESULTS: Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by STI571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by MTT assay. CONCLUSION: Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by STI571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.
Authors: Andrey Frolov; Santiago Chahwan; Michael Ochs; Juan Pablo Arnoletti; Zhong-Zong Pan; Olga Favorova; Jonathan Fletcher; Margaret von Mehren; Burton Eisenberg; Andrew K Godwin Journal: Mol Cancer Ther Date: 2003-08 Impact factor: 6.261
Authors: John M L Ebos; Jennifer Tran; Zubin Master; Daniel Dumont; Junia V Melo; Elisabeth Buchdunger; Robert S Kerbel Journal: Mol Cancer Res Date: 2002-12 Impact factor: 5.852
Authors: Juan Angel Fresno Vara; Enrique Casado; Javier de Castro; Paloma Cejas; Cristóbal Belda-Iniesta; Manuel González-Barón Journal: Cancer Treat Rev Date: 2004-04 Impact factor: 12.111