Enhanced expression of VEGF following bFGF inhibition in non-small cell lung cancer cell lines.
Inhibition of basic fibroblast growth factor (bFGF) leads to decreased proliferation of non-small cell lung cancer (NSCLC) cell lines. Although it is well known that bFGF stimulates vascular endothelial growth factor (VEGF) secretion, the influence of bFGF-inhibition is unclear. We therefore investigated the influence of bFGF inhibition on VEGF gene expression and secretion in NSCLC cell lines. In our experiments we demonstrated that inhibition of bFGF gene and protein expression induced increased secretion of VEGF. We also observed an increase of VEGF gene expression in these cells. Furthermore, inhibition of bFGF activated the p42/p44 mitogen-activated protein kinase (MAPK). These results demonstrate that inhibition of bFGF appears to stimulate VEGF production in a p42/44 MAPK-dependent manner. These findings suggest that inhibition of bFGF alone is not a promising strategy to inhibit angiogenesis.
Kuhn
Hartmut
H
Department of Respiratory Medicine, University of Leipzig, Germany. kuhnh@medizin.uni-leipzig.de
Konrad
Jana
J
Holtz
Silke
S
Salameh
Aida
A
Gessner
Christian
C
Hammerschmidt
Stefan
S
Wirtz
Hubert
H
D000911:Antibodies, Monoclonal; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense; D015398:Signal Transduction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D020319:Oligodeoxyribonucleotides, Antisense; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3