Document Type
Article
Publication Date
April 2005
Abstract
PURPOSE: To determine the effect of reducing MAP kinase phosphatase-1 (MKP-1) 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 ALL 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.
Recommended Citation
Abrams, Marc T.; Robertson, Noreen; Litwack, Gerald; and Wickstrom, Eric, "Evaluation of glucocorticoid sensitivity in 697 pre-B acute lymphoblastic leukemia cells after overexpression or silencing of MAP Kinase Phosphotase-1" (2005). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 1.
https://jdc.jefferson.edu/bmpfp/1
Comments
Author's final version prior to publication.
Published in: The Journal of Cancer Research and Clinical Oncology, 131(6): 347-54, June 2005. The original publication is available at http://www.springerlink.com/openurl.asp?genre=article&id=doi:10.1007/s00432-004-0659-3