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.

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