Tumorigenesis promotes Mdm4-S overexpression
| Autor: | Shunbin Xiong, Guillermina Lozano, Alfonso Quintás-Cardama, Vinod Pant, Neeraj K. Aryal, M. James You, Connie A. Larsson |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Male RNA Splicing Gene Expression Cell Cycle Proteins Mice Transgenic medicine.disease_cause Polymorphism Single Nucleotide 03 medical and health sciences splicing Mice Cell Line Tumor Leukemia Myelogenous Chronic BCR-ABL Positive Proto-Oncogene Proteins Gene expression medicine Animals Humans Gene Mdmx Aged Chromosome Aberrations Mutation biology business.industry Alternative splicing Mdm4-S/Mdm4 Nuclear Proteins Middle Aged transgenic mouse Gene Expression Regulation Neoplastic Disease Models Animal 030104 developmental biology Cell Transformation Neoplastic Oncology RNA splicing Immunology biology.protein Cancer research Mdm2 Female Carcinogenesis business CLL Biomarkers Priority Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Disruption of the p53 tumor suppressor pathway is a primary cause of tumorigenesis. In addition to mutation of the p53 gene itself, overexpression of major negative regulators of p53, MDM2 and MDM4, also act as drivers for tumor development. Recent studies suggest that expression of splice variants of Mdm2 and Mdm4 may be similarly involved in tumor development. In particular, multiple studies show that expression of a splice variant of MDM4, MDM4-S correlates with tumor aggressiveness and can be used as a prognostic marker in different tumor types. However, in the absence of prospective studies, it is not clear whether expression of MDM4-S in itself is oncogenic or is simply an outcome of tumorigenesis. Here we have examined the role of Mdm4-S in tumor development in a transgenic mouse model. Our results suggest that splicing of Mdm4 does not promote tumor development and does not cooperate with other oncogenic insults to alter tumor latency or aggressiveness. We conclude that Mdm4-S overexpression is a consequence of splicing defects in tumor cells rather than a cause of tumor evolution. |
| Databáze: | OpenAIRE |
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