Hypoglycemia-induced AP-1 transcription factor and basic fibroblast growth factor gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells

Mol Cell Biochem. 1996 Feb 23;155(2):163-71. doi: 10.1007/BF00229313.


We investigated the effect of hypoglycemic treatment on the activation of the AP-1 transcription factors and the regulation of basic fibroblast growth factor (bFGF) gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. Northern blot and gel mobility shift assays showed that hypoglycemic treatment induced c-jun and c-fos gene expression, AP-1 binding activity, as well as bFGF gene expression. Moreover, transfected cells expressing high levels of abnormal c-Jun protein exhibited a reduction in the bFGF protein levels compared to parental cells. A potent protein kinase C (PKC) inhibitor, H-7 (60 micrograms/ml) suppressed the stress-induced bFGF gene expression. Our study also demonstrated that H-7 did not facilitate the decay of bFGF mRNA. Thus, the suppression of bFGF gene expression by treatment with H-7 was due to the effect of the drug on the synthesis of bFGF mRNA rather than the stability of bFGF mRNA. Our data suggest that hypoglycemia-induced bFGF gene expression is mediated through the activation of PKC and the AP-1 transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Base Sequence
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Enzyme Inhibitors / pharmacology
  • Fibroblast Growth Factor 2 / genetics*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, fos
  • Genes, jun
  • Humans
  • Hypoglycemia / metabolism*
  • Isoquinolines / pharmacology
  • Molecular Sequence Data
  • Piperazines / pharmacology
  • Protein Binding
  • Protein Kinase C / antagonists & inhibitors
  • Transcription Factor AP-1 / genetics*
  • Tumor Cells, Cultured


  • Enzyme Inhibitors
  • Isoquinolines
  • Piperazines
  • Transcription Factor AP-1
  • Fibroblast Growth Factor 2
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Protein Kinase C