CREB regulates AChE-R-induced proliferation of human glioblastoma cells

Neoplasia. 2004 May-Jun;6(3):279-86. doi: 10.1593/neo.3424.

Abstract

The cyclic adenosine monophosphate (AMP) response element-binding protein, CREB, often modulates stress responses. Here, we report that CREB suppresses the glioblastoma proliferative effect of the stress-induced acetylcholinesterase variant, AChE-R. In human U87MG glioblastoma cells, AChE-R formed a triple complex with protein kinase C (PKC) epsilon and the scaffold protein RACK1, enhanced PKCepsilon phosphorylation, and facilitated BrdU incorporation. Either overexpressed CREB, or antisense destruction of AChE-R mRNA, PKC, or protein kinase A (PKA) inhibitors-but not CREB combined with PKC inhibition suppressed-this proliferation, suggesting that CREB's repression of this process involves a PKC-mediated pathway, whereas impaired CREB regulation allows AChE-R-induced, PKA-mediated proliferation of glioblastoma tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Acetylcholinesterase / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclic AMP Response Element-Binding Protein
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • GTP-Binding Proteins
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology*
  • Humans
  • Multiprotein Complexes / metabolism
  • Neoplasm Proteins / metabolism
  • Oligonucleotides, Antisense / pharmacology
  • Phosphorylation
  • Protein Binding
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein Kinase C-epsilon
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Multiprotein Complexes
  • Neoplasm Proteins
  • Oligonucleotides, Antisense
  • RACK1 protein, human
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Transcription Factors
  • Cyclic AMP-Dependent Protein Kinases
  • PRKCE protein, human
  • Protein Kinase C
  • Protein Kinase C-epsilon
  • Acetylcholinesterase
  • GTP-Binding Proteins