Evaluation of Glucocorticoid Sensitivity in 697 Pre-B Acute Lymphoblastic Leukemia Cells After Overexpression or Silencing of MAP Kinase Phosphatase-1

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2005 Apr 28

PMID 15856297

Citations 5

Authors

Marc T Abrams

Noreen M Robertson

Gerald Litwack

Eric Wickstrom

Affiliations

Soon will be listed here.

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.

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