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Checkpoint kinase 1 (CHK1) plays a key role in genome surveillance and integrity throughout the cell cycle. Selective inhibitors of CHK1 (CHK1i) are undergoing clinical evaluation for various human malignancies, including neuroblastoma. In this study, one CHK1i-sensitive neuroblastoma cell line, CHP134, was investigated, which characteristically carries MYCN amplification and a chromosome deletion within the 10q region. Among several cancer-related genes in the chromosome 10q region, mRNA expression of fibroblast growth factor receptor 2 (FGFR2) was altered in CHP134 cells and associated with an unfavorable prognosis of patients with neuroblastoma. Induced expression of FGFR2 in CHP134 cells reactivated downstream MEK/ERK signaling and resulted in cells resistant to CHK1i-mediated cell growth inhibition. Consistently, the MEK1/2 inhibitor, trametinib, potentiated CHK1 inhibitor-mediated cell death in these cells. These results suggested that FGFR2 loss might be prone to highly effective CHK1i treatment. In conclusion, extreme cellular dependency of ERK activation may imply a possible application for the MEK1/2 inhibitor, either as a single inhibitor or in combination with CHK1i in MYCN-amplified neuroblastomas.
Pubmed ID: 34807483 RIS Download
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Repository of raw sequencing data from next generation of sequencing platforms including including Roche 454 GS System, Illumina Genome Analyzer, Applied Biosystems SOLiD System, Helicos Heliscope, Complete Genomics, and Pacific Biosciences SMRT. In addition to raw sequence data, SRA now stores alignment information in form of read placements on reference sequence. Data submissions are welcome. Archive of high throughput sequencing data,part of international partnership of archives (INSDC) at NCBI, European Bioinformatics Institute and DNA Database of Japan. Data submitted to any of this three organizations are shared among them.
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on March 17,2022. Genome databases for vertebrates and other eukaryotic species. Analysis and annotation maintained on current data.Distribution of analysis to other bioinformatics laboratories. Ensembl concentrates on vertebrate genomes, but other groups have adapted system for use with plant and fungal genomes (see Powered by Ensembl list on website).
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View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
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