Protein kinase C signalling pathway is involved in the regulation of vascular endothelial growth factor expression in human bladder transitional carcinoma cells

E Chabannes; S Fauconnet; S Bernardini; H Wallerand; G Adessi; H Bittard

doi:10.1016/s0898-6568(01)00184-x

Protein kinase C signalling pathway is involved in the regulation of vascular endothelial growth factor expression in human bladder transitional carcinoma cells

Cell Signal. 2001 Aug;13(8):585-91. doi: 10.1016/s0898-6568(01)00184-x.

Authors

E Chabannes¹, S Fauconnet, S Bernardini, H Wallerand, G Adessi, H Bittard

Affiliation

¹ Service d'Urologie, Hôpital Saint-Jacques, 2, Place St. Jacques, 25000, Besancon, France. [email protected]

PMID: 11483411
DOI: 10.1016/s0898-6568(01)00184-x

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor associated with the growth and metastasis of various cancers and plays a prominent role in vesical angiogenesis regulation. In this study, we investigated the effect of the phorbol 12-myristate 13-acetate (PMA) on the expression of VEGF in human bladder transitional carcinoma cells (RT4). RT4 cells expressed three VEGF isoforms (VEGF(189), VEGF(165), VEGF(121)). PMA increased VEGF mRNA expression time-dependently with a peak at 4 h. PMA increased the half-life of VEGF mRNA. The amount of VEGF protein in conditioned media was increased by PMA in a dose-dependent manner with a maximal effect at 10(-7) M. Staurosporine and calphostin C (PKC inhibitors) decreased PMA-induced VEGF mRNA expression as opposed to protein kinase A or cyclic nucleotide-dependent protein kinase inhibitors. Thus, in RT4 cells, VEGF expression is up-regulated by PMA via the PKC signalling pathway and according to a posttranscriptional mechanism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Transitional Cell / metabolism*
Culture Media, Conditioned / chemistry
Endothelial Growth Factors / biosynthesis*
Endothelial Growth Factors / genetics
Enzyme Inhibitors / pharmacology
Humans
Lymphokines / biosynthesis*
Lymphokines / genetics
Protein Isoforms / biosynthesis
Protein Isoforms / genetics
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / physiology*
RNA Stability / drug effects
RNA, Messenger / biosynthesis
Signal Transduction*
Tetradecanoylphorbol Acetate / pharmacology
Transcription, Genetic
Tumor Cells, Cultured
Up-Regulation
Urinary Bladder Neoplasms / metabolism*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors

Substances

Culture Media, Conditioned
Endothelial Growth Factors
Enzyme Inhibitors
Lymphokines
Protein Isoforms
RNA, Messenger
VEGFA protein, human
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Protein Kinase C
Tetradecanoylphorbol Acetate