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Neuroblastoma is a malignant childhood cancer arising from the embryonic sympathoadrenal lineage of the neural crest. Retinoic acid (RA) is included in the multimodal therapy of patients with high-risk neuroblastoma to eliminate minimal residual disease. However, the formation of RA-resistant cells substantially lowers 5-year overall survival rates. To examine mechanisms that lead to treatment failure, we chose human SH-SY5Y cells, which are known to tolerate incubation with RA by activating the survival kinases Akt and extracellular signal-regulated kinase 1/2. Characterization of downstream pathways showed that both kinases increased the phosphorylation of the ubiquitin ligase mouse double minute homolog 2 (Mdm2) and thereby enhanced p53 degradation. When p53 signaling was sustained by blocking complex formation with Mdm2 or enhancing c-Jun N-terminal kinase (JNK) activation, cell viability was significantly reduced. In addition, Akt-mediated phosphorylation of the cell-cycle regulator p21 stimulated complex formation with caspase-3, which also contributed to cell protection. Thus, treatment with RA augmented survival signaling and attenuated basal apoptotic pathways in SH-SY5Y cells, which increased cell viability.
Pubmed ID: 30320919 RIS Download
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This polyclonal targets MDM2, phospho (Ser166)
View all literature mentionsThis polyclonal targets Phospho-p53 (Ser15)
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets BBC3
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets caspase-3
View all literature mentionsCell line SH-SY5Y is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets caspase-3
View all literature mentionsThis unknown targets IgG
View all literature mentionsCell line SH-SY5Y is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis polyclonal targets Phospho-p53 (Ser15)
View all literature mentionsThis polyclonal targets MDM2, phospho (Ser166)
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets BBC3
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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