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Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells.

Akagi M, Kawaguchi M, Liu W, McCarty MF, Takeda A, Fan F, Stoeltzing O, Parikh AA, Jung YD, Bucana CD, Mansfield PF, Hicklin DJ, Ellis LM - Br. J. Cancer (2003)

Bottom Line: Moreover, in EGF-R-positive NCI-N87 and ST-2 cells, EGF induced both NRP-1 and VEGF mRNA expression.The treatment of NCI-N87 cells with EGF resulted in increases in phosphorylation of Erk1/2, Akt, and P38.Blockade of the Erk, phosphatidylinositol-3 kinase/Akt, or P38 pathways in this cell line prevented EGF induction of NRP-1 and VEGF.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.

ABSTRACT
The epidermal growth factor receptor (EGF-R) pathway plays a pivotal role in the progression of human gastric cancer. The angiogenic factor vascular endothelial growth factor (VEGF) has been shown to be induced by EGF in various cancer cell lines. Neuropilin-1 (NRP-1) acts as a coreceptor for VEGF-165 and increases its affinity for VEGF receptor 2 (VEGFR-2) in endothelial cells. Furthermore, NRP-1 has been found to be expressed by tumour cells and has been shown to enhance tumour angiogenesis and growth in preclinical models. We examined the expression of NRP-1 mRNA and EGF-R protein in seven human gastric cancer cell lines. NRP-1 expression was expressed in five of seven cell lines, and EGF-R expression closely mirrored NRP-1 expression. Moreover, in EGF-R-positive NCI-N87 and ST-2 cells, EGF induced both NRP-1 and VEGF mRNA expression. C225, a monoclonal antibody to EGF-R, blocked EGF-induced NRP-1 and VEGF expression in NCI-N87 cells in a dose-dependent manner. The treatment of NCI-N87 cells with EGF resulted in increases in phosphorylation of Erk1/2, Akt, and P38. Blockade of the Erk, phosphatidylinositol-3 kinase/Akt, or P38 pathways in this cell line prevented EGF induction of NRP-1 and VEGF. These results suggest that regulation of NRP-1 expression in human gastric cancer is intimately associated with the EGF/EGF-R system. Activation of EGF-R might contribute to gastric cancer angiogenesis by a mechanism that involves upregulation of VEGF and NRP-1 expression via multiple signalling pathways.

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Effect of Erk1/2, Akt, and P38 MAPK inhibition on NRP-1 and VEGF induction by EGF in NCI-N87 cells. The cells were incubated in 5% serum-containing medium overnight and then were pretreated with 50 μM PD98059, 10 μM U0126, 200 nM wortmannin, or 25 μM SB203580 for 1 h in 1% FBS-containing medium. EGF (50 ng ml−1) was then added for 24 h. Control cells were not treated with EGF (lane 1) and cells treated with EGF without addition of signalling inhibitors served as another internal control (lane 2). Total RNA was extracted, and Northern blot analysis was performed. Blockade of the Erk1/2, Akt or P38 pathways all led variable decreases in NRP-1 and VEGF mRNA expression.
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fig5: Effect of Erk1/2, Akt, and P38 MAPK inhibition on NRP-1 and VEGF induction by EGF in NCI-N87 cells. The cells were incubated in 5% serum-containing medium overnight and then were pretreated with 50 μM PD98059, 10 μM U0126, 200 nM wortmannin, or 25 μM SB203580 for 1 h in 1% FBS-containing medium. EGF (50 ng ml−1) was then added for 24 h. Control cells were not treated with EGF (lane 1) and cells treated with EGF without addition of signalling inhibitors served as another internal control (lane 2). Total RNA was extracted, and Northern blot analysis was performed. Blockade of the Erk1/2, Akt or P38 pathways all led variable decreases in NRP-1 and VEGF mRNA expression.

Mentions: We next selectively blocked the Erk1/2, Akt, or P38 MAPK pathways to determine which pathway was essential for EGF induction of NRP-1 and VEGF mRNA expression in NCI-N87 cells. The results of Northern blot analysis are shown in Figure 5Figure 5


Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells.

Akagi M, Kawaguchi M, Liu W, McCarty MF, Takeda A, Fan F, Stoeltzing O, Parikh AA, Jung YD, Bucana CD, Mansfield PF, Hicklin DJ, Ellis LM - Br. J. Cancer (2003)

Effect of Erk1/2, Akt, and P38 MAPK inhibition on NRP-1 and VEGF induction by EGF in NCI-N87 cells. The cells were incubated in 5% serum-containing medium overnight and then were pretreated with 50 μM PD98059, 10 μM U0126, 200 nM wortmannin, or 25 μM SB203580 for 1 h in 1% FBS-containing medium. EGF (50 ng ml−1) was then added for 24 h. Control cells were not treated with EGF (lane 1) and cells treated with EGF without addition of signalling inhibitors served as another internal control (lane 2). Total RNA was extracted, and Northern blot analysis was performed. Blockade of the Erk1/2, Akt or P38 pathways all led variable decreases in NRP-1 and VEGF mRNA expression.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376351&req=5

fig5: Effect of Erk1/2, Akt, and P38 MAPK inhibition on NRP-1 and VEGF induction by EGF in NCI-N87 cells. The cells were incubated in 5% serum-containing medium overnight and then were pretreated with 50 μM PD98059, 10 μM U0126, 200 nM wortmannin, or 25 μM SB203580 for 1 h in 1% FBS-containing medium. EGF (50 ng ml−1) was then added for 24 h. Control cells were not treated with EGF (lane 1) and cells treated with EGF without addition of signalling inhibitors served as another internal control (lane 2). Total RNA was extracted, and Northern blot analysis was performed. Blockade of the Erk1/2, Akt or P38 pathways all led variable decreases in NRP-1 and VEGF mRNA expression.
Mentions: We next selectively blocked the Erk1/2, Akt, or P38 MAPK pathways to determine which pathway was essential for EGF induction of NRP-1 and VEGF mRNA expression in NCI-N87 cells. The results of Northern blot analysis are shown in Figure 5Figure 5

Bottom Line: Moreover, in EGF-R-positive NCI-N87 and ST-2 cells, EGF induced both NRP-1 and VEGF mRNA expression.The treatment of NCI-N87 cells with EGF resulted in increases in phosphorylation of Erk1/2, Akt, and P38.Blockade of the Erk, phosphatidylinositol-3 kinase/Akt, or P38 pathways in this cell line prevented EGF induction of NRP-1 and VEGF.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.

ABSTRACT
The epidermal growth factor receptor (EGF-R) pathway plays a pivotal role in the progression of human gastric cancer. The angiogenic factor vascular endothelial growth factor (VEGF) has been shown to be induced by EGF in various cancer cell lines. Neuropilin-1 (NRP-1) acts as a coreceptor for VEGF-165 and increases its affinity for VEGF receptor 2 (VEGFR-2) in endothelial cells. Furthermore, NRP-1 has been found to be expressed by tumour cells and has been shown to enhance tumour angiogenesis and growth in preclinical models. We examined the expression of NRP-1 mRNA and EGF-R protein in seven human gastric cancer cell lines. NRP-1 expression was expressed in five of seven cell lines, and EGF-R expression closely mirrored NRP-1 expression. Moreover, in EGF-R-positive NCI-N87 and ST-2 cells, EGF induced both NRP-1 and VEGF mRNA expression. C225, a monoclonal antibody to EGF-R, blocked EGF-induced NRP-1 and VEGF expression in NCI-N87 cells in a dose-dependent manner. The treatment of NCI-N87 cells with EGF resulted in increases in phosphorylation of Erk1/2, Akt, and P38. Blockade of the Erk, phosphatidylinositol-3 kinase/Akt, or P38 pathways in this cell line prevented EGF induction of NRP-1 and VEGF. These results suggest that regulation of NRP-1 expression in human gastric cancer is intimately associated with the EGF/EGF-R system. Activation of EGF-R might contribute to gastric cancer angiogenesis by a mechanism that involves upregulation of VEGF and NRP-1 expression via multiple signalling pathways.

Show MeSH
Related in: MedlinePlus