Original Paper

Journal of Cancer Research and Clinical Oncology

, Volume 131, Issue 6, pp 347-354

Evaluation of glucocorticoid sensitivity in 697 pre-B acute lymphoblastic leukemia cells after overexpression or silencing of MAP kinase phosphatase-1

  • Marc T. AbramsAffiliated withDepartment of Biochemistry and Molecular Pharmacology, Thomas Jefferson University
  • , Noreen M. RobertsonAffiliated withA.J. Drexel Institute of Basic and Applied Protein Science, Drexel University School of Medicine
  • , Gerald LitwackAffiliated withDepartment of Biochemistry and Molecular Pharmacology, Thomas Jefferson University
  • , Eric WickstromAffiliated withDepartment of Biochemistry and Molecular Pharmacology, Thomas Jefferson University Email author 

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Abstract

Purpose

To determine the effect of modulating MAP kinase phosphatase-1 (MKP-1) expression levels on cell death induced by glucocorticoid (GC) or hydroxyurea (HU) treatment in the human pre-B acute lymphoblastic leukemia cell line 697.

Methods

Stable MKP-1 overexpressing transformants of the 697 pre-B acute lymphoblastic leukemia cell line were created and tested for sensitivity to the GC triamcinolone acetonide (TA) and HU, and compared to a control 697 cell line containing normal MKP-1 expression levels. Small interfering RNAs (siRNAs) were designed to inhibit MKP-1 expression and evaluated for their effect on GC-mediated cell death.

Results

MKP-1 overexpression caused a phenotype of partial resistance to HU-induced apoptosis but not to GC-induced apoptosis. Electroporation of siRNAs effectively silenced MKP-1 expression, and increased sensitivity to TA by 9.6±1.9%.

Conclusions

Because MKP-1 protects certain tumor cells from chemotherapy-induced apoptosis, its inhibition is being considered as a possible strategy for combination cancer therapy. However, this study suggests that while MKP-1 inhibition may improve the efficacy of DNA damaging agents, it may have only limited utility in combination with glucocorticoids.

Keywords

Glucocorticoid Apoptosis MKP-1 siRNA ALL