Implication of Egr-1 in trifluoperazine-induced growth inhibition in human U87MG glioma cells

Exp Mol Med. 2004 Aug 31;36(4):380-6. doi: 10.1038/emm.2004.50.

Abstract

The early growth response gene-1 (Egr-1) is a tumor suppressor which plays an important role in cell growth, differentiation and apoptosis. Egr-1 has been shown to be down-regulated in many types of tumor tissues. Trifluoperazine (TFP), a phenothiazine class of antipsychotics, restored serum-induced Egr-1 expression in several cancer cell lines. We investigated the effect of Egr-1 expression on the TFP-induced inhibition of cell growth. Ectopic expression of Egr-1 enhanced the TFP-induced antiproliferative activity and downregulated cyclin D1 level in U87MG glioma cells. Our results suggest that antipsychotics TFP exhibits antiproliferative activity through up-regulation of Egr-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Proliferation / drug effects
  • Cyclin D1 / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Early Growth Response Protein 1
  • Gene Expression
  • Glioma / metabolism*
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Promoter Regions, Genetic / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Trifluoperazine / pharmacology*
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • Transcription Factors
  • Cyclin D1
  • Trifluoperazine