A deficiency in Mdm2 binding protein inhibits Myc-induced B-cell proliferation and lymphomagenesis.

Odvody J, Vincent T, Arrate MP, Grieb B, Wang S, Garriga J, Lozano G, Iwakuma T, Haines DS, Eischen CM
Oncogene. 2010 29 (22): 3287-96

PMID: 20305689 · PMCID: PMC2880662 · DOI:10.1038/onc.2010.82

Mdm2 binding protein (MTBP) has been implicated in cell-cycle arrest and the Mdm2/p53 tumor suppressor pathway through its interaction with Mdm2. To determine the function of MTBP in tumorigenesis and its potential role in the Mdm2/p53 pathway, we crossed Mtbp-deficient mice to Emu-myc transgenic mice, in which overexpression of the oncogene c-Myc induces B-cell lymphomas primarily through inactivation of the Mdm2/p53 pathway. We report that Myc-induced B-cell lymphoma development in Mtbp heterozygous mice was profoundly delayed. Surprisingly, reduced levels of Mtbp did not lead to an increase in B-cell apoptosis or affect Mdm2. Instead, an Mtbp deficiency inhibited Myc-induced proliferation and the upregulation of Myc target genes necessary for cell growth. Consistent with a role in proliferation, Mtbp expression was induced by Myc and other factors that promote cell-cycle progression and was elevated in lymphomas from humans and mice. Therefore, Mtbp functioned independent of Mdm2 and was a limiting factor for the proliferative and transforming functions of Myc. Thus, Mtbp is a previously unrecognized regulator of Myc-induced tumorigenesis.

MeSH Terms (17)

Animals Apoptosis B-Lymphocytes Carrier Proteins Cell Growth Processes Cells, Cultured Female Genes, myc Genes, Tumor Suppressor Humans Lymphoma, B-Cell Male Mice Mice, Inbred C57BL Mice, Transgenic Proto-Oncogene Proteins c-mdm2 Tumor Suppressor Protein p53

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