Protein kinase C mediates induced secretion of vascular endothelial growth factor by human glioma cells

Jui Chang Tsai, Lee Jene Teng, Chin Tin Chen, Tse-Ming Hong, Corey K. Goldman, G. Yancey Gillespie

研究成果: Article

11 引文 (Scopus)

摘要

To understand how vascular endothelial growth factor (VEGF) production is activated in malignant glioma cells, we employed protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors to evaluate the extent to which these protein kinases were involved in signal transduction leading to VEGF production. PTK inhibitors blocked glioma proliferation and epidermal growth factor (EGF)-induced VEGF secretion, while H-7, a PKC inhibitor, inhibited both EGF-induced and baseline VEGF secretion. Phorbol 12-myristate 13-acetate (PMA), a non-specific activator of PKC, induced VEGF secretion by glioma cells, which was enhanced by calcium ionophore A23187, but completely blocked after prolonged treatment of cells with 1μM PMA, by presumably depleting PKC. All inhibitors (genistein, AG18, AG213, H-7, prolonged PMA treatment) which inhibited EGF-induced VEGF secretion in glioma cells also inhibited cell proliferation at similar concentrations. However, PKC inhibition only blocked 50% of the VEGF secretion induced by growth factors (EGF, platelet-derived growth factor-BB, or basic fibroblast growth factor). This reserve capacity could be ascribed to a PKC-independent effect, or to PKC isoenzymes not down-regulated by PMA. These findings extend our previous assertion that VEGF secretion is tightly coupled with proliferation by suggesting that activation of convergent growth factor signaling pathways will lead to increased glioma VEGF secretion. Understanding of signal transduction of growth factor-induced VEGF secretion should provide a rational basis for the development of novel strategies for therapy.

原文English
頁(從 - 到)952-960
頁數9
期刊Biochemical and Biophysical Research Communications
309
發行號4
DOIs
出版狀態Published - 2003 十月 3

指紋

Glioma
Protein Kinase C
Vascular Endothelial Growth Factor A
Epidermal Growth Factor
Acetates
Protein Kinase Inhibitors
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Intercellular Signaling Peptides and Proteins
Signal transduction
Protein C Inhibitor
Protein-Tyrosine Kinases
Signal Transduction
human VEGFA protein
Calcium Ionophores
Genistein
Calcimycin
Cell proliferation
Fibroblast Growth Factor 2
Protein Kinases
Isoenzymes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

引用此文

Tsai, Jui Chang ; Teng, Lee Jene ; Chen, Chin Tin ; Hong, Tse-Ming ; Goldman, Corey K. ; Gillespie, G. Yancey. / Protein kinase C mediates induced secretion of vascular endothelial growth factor by human glioma cells. 於: Biochemical and Biophysical Research Communications. 2003 ; 卷 309, 編號 4. 頁 952-960.
@article{59250a207c394b778f714fd247a9115a,
title = "Protein kinase C mediates induced secretion of vascular endothelial growth factor by human glioma cells",
abstract = "To understand how vascular endothelial growth factor (VEGF) production is activated in malignant glioma cells, we employed protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors to evaluate the extent to which these protein kinases were involved in signal transduction leading to VEGF production. PTK inhibitors blocked glioma proliferation and epidermal growth factor (EGF)-induced VEGF secretion, while H-7, a PKC inhibitor, inhibited both EGF-induced and baseline VEGF secretion. Phorbol 12-myristate 13-acetate (PMA), a non-specific activator of PKC, induced VEGF secretion by glioma cells, which was enhanced by calcium ionophore A23187, but completely blocked after prolonged treatment of cells with 1μM PMA, by presumably depleting PKC. All inhibitors (genistein, AG18, AG213, H-7, prolonged PMA treatment) which inhibited EGF-induced VEGF secretion in glioma cells also inhibited cell proliferation at similar concentrations. However, PKC inhibition only blocked 50{\%} of the VEGF secretion induced by growth factors (EGF, platelet-derived growth factor-BB, or basic fibroblast growth factor). This reserve capacity could be ascribed to a PKC-independent effect, or to PKC isoenzymes not down-regulated by PMA. These findings extend our previous assertion that VEGF secretion is tightly coupled with proliferation by suggesting that activation of convergent growth factor signaling pathways will lead to increased glioma VEGF secretion. Understanding of signal transduction of growth factor-induced VEGF secretion should provide a rational basis for the development of novel strategies for therapy.",
author = "Tsai, {Jui Chang} and Teng, {Lee Jene} and Chen, {Chin Tin} and Tse-Ming Hong and Goldman, {Corey K.} and Gillespie, {G. Yancey}",
year = "2003",
month = "10",
day = "3",
doi = "10.1016/j.bbrc.2003.08.106",
language = "English",
volume = "309",
pages = "952--960",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

Protein kinase C mediates induced secretion of vascular endothelial growth factor by human glioma cells. / Tsai, Jui Chang; Teng, Lee Jene; Chen, Chin Tin; Hong, Tse-Ming; Goldman, Corey K.; Gillespie, G. Yancey.

於: Biochemical and Biophysical Research Communications, 卷 309, 編號 4, 03.10.2003, p. 952-960.

研究成果: Article

TY - JOUR

T1 - Protein kinase C mediates induced secretion of vascular endothelial growth factor by human glioma cells

AU - Tsai, Jui Chang

AU - Teng, Lee Jene

AU - Chen, Chin Tin

AU - Hong, Tse-Ming

AU - Goldman, Corey K.

AU - Gillespie, G. Yancey

PY - 2003/10/3

Y1 - 2003/10/3

N2 - To understand how vascular endothelial growth factor (VEGF) production is activated in malignant glioma cells, we employed protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors to evaluate the extent to which these protein kinases were involved in signal transduction leading to VEGF production. PTK inhibitors blocked glioma proliferation and epidermal growth factor (EGF)-induced VEGF secretion, while H-7, a PKC inhibitor, inhibited both EGF-induced and baseline VEGF secretion. Phorbol 12-myristate 13-acetate (PMA), a non-specific activator of PKC, induced VEGF secretion by glioma cells, which was enhanced by calcium ionophore A23187, but completely blocked after prolonged treatment of cells with 1μM PMA, by presumably depleting PKC. All inhibitors (genistein, AG18, AG213, H-7, prolonged PMA treatment) which inhibited EGF-induced VEGF secretion in glioma cells also inhibited cell proliferation at similar concentrations. However, PKC inhibition only blocked 50% of the VEGF secretion induced by growth factors (EGF, platelet-derived growth factor-BB, or basic fibroblast growth factor). This reserve capacity could be ascribed to a PKC-independent effect, or to PKC isoenzymes not down-regulated by PMA. These findings extend our previous assertion that VEGF secretion is tightly coupled with proliferation by suggesting that activation of convergent growth factor signaling pathways will lead to increased glioma VEGF secretion. Understanding of signal transduction of growth factor-induced VEGF secretion should provide a rational basis for the development of novel strategies for therapy.

AB - To understand how vascular endothelial growth factor (VEGF) production is activated in malignant glioma cells, we employed protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors to evaluate the extent to which these protein kinases were involved in signal transduction leading to VEGF production. PTK inhibitors blocked glioma proliferation and epidermal growth factor (EGF)-induced VEGF secretion, while H-7, a PKC inhibitor, inhibited both EGF-induced and baseline VEGF secretion. Phorbol 12-myristate 13-acetate (PMA), a non-specific activator of PKC, induced VEGF secretion by glioma cells, which was enhanced by calcium ionophore A23187, but completely blocked after prolonged treatment of cells with 1μM PMA, by presumably depleting PKC. All inhibitors (genistein, AG18, AG213, H-7, prolonged PMA treatment) which inhibited EGF-induced VEGF secretion in glioma cells also inhibited cell proliferation at similar concentrations. However, PKC inhibition only blocked 50% of the VEGF secretion induced by growth factors (EGF, platelet-derived growth factor-BB, or basic fibroblast growth factor). This reserve capacity could be ascribed to a PKC-independent effect, or to PKC isoenzymes not down-regulated by PMA. These findings extend our previous assertion that VEGF secretion is tightly coupled with proliferation by suggesting that activation of convergent growth factor signaling pathways will lead to increased glioma VEGF secretion. Understanding of signal transduction of growth factor-induced VEGF secretion should provide a rational basis for the development of novel strategies for therapy.

UR - http://www.scopus.com/inward/record.url?scp=0141453284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141453284&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2003.08.106

DO - 10.1016/j.bbrc.2003.08.106

M3 - Article

C2 - 13679066

AN - SCOPUS:0141453284

VL - 309

SP - 952

EP - 960

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -