Regulation of the MDR1 promoter by cyclic AMP-dependent protein kinase and transcription factor Sp1

Int J Oncol. 1998 Feb;12(2):383-6. doi: 10.3892/ijo.12.2.383.


The expression of multidrug-resistance (MDR) in breast carcinoma cell line MCF-7/ADR50 is primarily dependent on the transcriptional activation of the MDR1 gene. We now report that MDR in this cell line is partially reversed by the type I cAMP-dependent protein kinase (PKA) inhibitor, 8-Cl-cAMP. MDR1 promoter activity was also regulated through a PKA-dependent pathway and was inhibited by 8-Cl-cAMP, and stimulated by the enantiomeric agonist, SpcAMP[S]. MDR1 promoter activity through an Sp1 response element was stimulated by exogenous Sp1, a factor that we have shown to be activated by PKA. These results indicate that MDR1 promoter activity is linked to the cAMP/PKA signaling pathway, and that PKA antagonists may be useful for reversing the multidrug-resistant phenotype.

Publication types

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

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / analogs & derivatives*
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / pharmacology*
  • Doxorubicin / therapeutic use
  • Drosophila
  • Drug Resistance, Multiple
  • Genes, MDR / drug effects*
  • Phenotype
  • Promoter Regions, Genetic / drug effects*
  • Sp1 Transcription Factor / pharmacology*
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured / drug effects


  • Sp1 Transcription Factor
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Doxorubicin
  • 8-chloro-cyclic adenosine monophosphate
  • Cyclic AMP-Dependent Protein Kinases