A deficiency in Mdm2 binding protein inhibits Myc-induced B-cell proliferation and lymphomagenesis
| Autor: | Dale S. Haines, Tomoo Iwakuma, Maria Pia Arrate, Tiffaney Vincent, Judit Garriga, Jessica Odvody, Shuo Wang, Brian C. Grieb, Christine M. Eischen, Guillermina Lozano |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Genetically modified mouse
Male p53 Cancer Research Lymphoma B-Cell Tumor suppressor gene Genes myc MTBP Apoptosis Mice Transgenic lymphoma Cell Growth Processes Myc Biology medicine.disease_cause Article 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Proto-Oncogene Proteins c-mdm2 Mdm2 Genetics medicine Animals Humans Genes Tumor Suppressor Molecular Biology Cells Cultured 030304 developmental biology 0303 health sciences B-Lymphocytes Oncogene Cell growth 3. Good health Mice Inbred C57BL 030220 oncology & carcinogenesis Cancer research biology.protein Female Tumor Suppressor Protein p53 Carcinogenesis Carrier Proteins |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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