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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Activation of MDR1 (P-glycoprotein) gene expression in human cells by protein kinase C agonists

P M Chaudhary1, I B Roninson

  • 1Department of Genetics, University of Illinois, Chicago 60612.

Oncology Research
|January 1, 1992
PubMed

Insights

Protein kinase C (PKC) activation by agents like TPA increases P-glycoprotein and MDR1 gene expression. This suggests a PKC-mediated pathway regulates multidrug resistance in various cell types.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • P-glycoprotein, encoded by the MDR1 gene, is a transmembrane efflux pump.
  • MDR1 expression is linked to multidrug resistance in tumors and chemotherapy resistance.
  • Elevated protein kinase C (PKC) is observed in some multidrug-resistant cells, but its role is unclear.

Purpose of the Study:

  • To investigate the effects of lymphocyte-activating agents on P-glycoprotein activity.
  • To determine the functional association of PKC with P-glycoprotein-mediated multidrug resistance.

Main Methods:

  • Studied P-glycoprotein activity in normal human lymphocytes using TPA, a PKC agonist.
  • Examined P-glycoprotein expression in leukemia and solid tumor cell lines.
  • Measured MDR1 gene expression at protein and RNA levels.
  • Utilized diacylglycerol (DAG) and staurosporine for further investigation.

Main Results:

  • TPA increased P-glycoprotein activity and levels in lymphocytes.
  • TPA elevated P-glycoprotein expression in various cancer cell lines.
  • MDR1 gene expression (mRNA and protein) increased upon TPA and DAG treatment.
  • PKC inhibitor staurosporine suppressed TPA/DAG-induced MDR1 expression.

Conclusions:

  • MDR1 gene expression appears to be regulated by a PKC-mediated pathway.
  • This pathway plays a role in the development of multidrug resistance in vitro and in vivo.

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