Differential effect of glucose deprivation on MAPK activation in drug sensitive human breast carcinoma MCF-7 and multidrug resistant MCF-7/ADR cells

Mol Cell Biochem. 1997 May;170(1-2):23-30. doi: 10.1023/a:1006890316102.

Abstract

We have investigated the effect of glucose deprivation treatment on the activation of mitogen activated protein kinases (MAPKs) in the drug-sensitive human breast carcinoma cells (MCF-7) and its drug resistant variant (MCF-7/ADR) cells. Western blots and in-gel kinase assays showed that glucose free medium was a strong stimulus for the activation of MAPK in MCF-7/ADR cells. No activation was seen in MCF-7 cells. MAPK was activated within 3 min of being in glucose free medium and it remained activated for over 1 h in MCF-7/ADR cells. After being returned to complete medium, 1 h was required for the MAPK to become deactivated. To investigate whether alternative sources of ATP could inhibit glucose deprivation induced MAPK activation, we added glutamine and glutamate to glucose deprived medium. The addition of glutamine did not reverse glucose deprivation induced MAPK activation in MCF-7/ADR cells. The addition of glutamate, however, decreased the MAPK activation and the length of time of activation. We observed an increase greater than three fold in MEK, Raf, Ras, and PKC activity with glucose deprivation in MCF-7/ADR cells. This suggests that glucose deprivation-induced MAPK activation is mediated through this signal transduction pathway.

Publication types

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

MeSH terms

  • Breast Neoplasms
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Doxorubicin / toxicity
  • Drug Resistance, Multiple*
  • Enzyme Activation / drug effects
  • Female
  • Glucose / pharmacology*
  • Glutamic Acid / pharmacology
  • Glutamine / pharmacology
  • Humans
  • Kinetics
  • MAP Kinase Kinase Kinase 1*
  • Protein Kinase C / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-raf
  • Signal Transduction
  • Tumor Cells, Cultured
  • ras Proteins / metabolism

Substances

  • Proto-Oncogene Proteins
  • Glutamine
  • Glutamic Acid
  • Doxorubicin
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • ras Proteins
  • Glucose