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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Inhibition of c-Jun N-terminal kinase by SP600125: a cDNA microarray analysis
Pierre Champelovier1, Michele El Atifi-Borel, Jean Paul Issartel
1Laboratoire de Cytologie, Département d'Anatomie et de Cytologie Pathologiques, CHU de Grenoble, Hopital A. Michallon, BP 217X, 38043 Grenoble cedex 09, France. PChampelovier@chu-grenoble.fr
Background:
In a previous investigation, we showed that the janus kinase (JNK) inhibitor SP600125 induced several phenotypic and genomic changes in leukemia cells. However, the molecular mechanisms that sustain these changes remain unknown. The purpose of the present study was to examine gene expression changes in THP-1 leukemia cells treated with SP600125.
Materials And Methods:
Gene expression levels were investigated using Affymetrix hybridization technology and quantitative reverse transcriptase polymerase chain reaction.
Results:
Affymetrix technology showed that the expression of 1,038 genes with a biological process description well known in gene ontology was modulated. Fifteen genes were related to kinases or phosphatases, 20 genes were involved in the cell cycle regulation, and 23 genes were involved in apoptosis. A network of 15 correlated genes was obtained showing a primordial role for the myelocytomatosis viral oncogene homolog (MYC).
Conclusion:
These findings show that SP600125 exhibits cytostatic and cytolytic activities through MYC gene modulation.
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