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GSE18204
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The antiapoptotic Bcl-2 family member Bfl-1 is upregulated in many human tumors in which NF-kB is implicated, and contributes significantly to tumor cell survival and chemoresistance. We previously found that NF-kB induces transcription of bfl-1, and that the Bfl-1 protein is also regulated by the ubiquitin-proteasome. However little is known of the role that dysregulation of Bfl-1 turnover plays in cancer. We found that ubiquitination-resistant mutants of Bfl-1 display increased stability and greatly accelerate tumor formation in a mouse model of leukemia/lymphoma. Gene expression profiling revealed that tyrosine kinase Lck is highly upregulated and activated in these tumors compared to the parental cells, as were several genes in the RANK signaling pathway, and leads to activation of the IKK, Akt and Erk signaling pathways, which are key mediators in cancer. Tumor assays with cells coexpressing constitutively active Lck with Bfl-1, or with tumor-derived cells following shRNA-mediated Lck knockdown, unveiled functional cooperation between Bfl-1 and Lck in leukemia/lymphomagenesis. These data demonstrate that ubiquitination is a critical mechanism for regulating Bfl-1 function, and suggest that mutations in bfl-1 or in the signaling pathways that control its ubiquitination may predispose to cancer. Additionally since bfl-1 is upregulated in many human hematopoietic tumors, these data suggest that strategies to promote Bfl-1 ubiquitination may improve therapy in drug-resistant tumors.
Publication Title
Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The objective of this analysis was to identify the genes that are differentially expressed between preadipocytes with low or high adipogenic capability
Publication Title
Amplification of Adipogenic Commitment by VSTM2A.
Sample Metadata Fields
Specimen part
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