RTVP-1 expression is regulated by SRF downstream of protein kinase C and contributes to the effect of SRF on glioma cell migration

Cell Signal. 2011 Dec;23(12):1936-43. doi: 10.1016/j.cellsig.2011.07.001. Epub 2011 Jul 12.

Abstract

Gliomas are characterized by increased infiltration into the surrounding normal brain tissue. We recently reported that RTVP-1 is highly expressed in gliomas and plays a role in the migration of these cells, however the regulation of RTVP-1 expression in these cells is not yet described. In this study we examined the role of PKC in the regulation of RTVP-1 expression and found that PMA and overexpression of PKCα and PKCε increased the expression of RTVP-1, whereas PKCδ exerted an opposite effect. Using the MatInspector software, we identified a SRF binding site on the RTVP-1 promoter. Chromatin immunoprecipitation (ChIP) assay revealed that SRF binds to the RTVP-1 promoter in U87 cells, and that this binding was significantly increased in response to serum addition. Moreover, silencing of SRF blocked the induction of RTVP-1 expression in response to serum. We found that overexpression of PKCα and PKCε increased the activity of the RTVP-1 promoter and the binding of SRF to the promoter. In contrast, overexpression of PKCδ blocked the increase in RTVP-1 expression in response to serum and the inhibitory effect of PKCδ was abrogated in cells expressing a SRFT160A mutant. SRF regulated the migration of glioma cells and its effect was partially mediated by RTVP-1. We conclude that RTVP-1 is a PKC-regulated gene and that this regulation is at least partly mediated by SRF. Moreover, RTVP-1 plays a role in the effect of SRF on glioma cell migration.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Glioma / metabolism
  • Glioma / physiopathology*
  • Humans
  • Isoenzymes / metabolism
  • Membrane Proteins
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Kinase C / metabolism*
  • Serum Response Factor / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • GLIPR1 protein, human
  • Isoenzymes
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Serum Response Factor
  • Protein Kinase C