The Role of MDM2 Amplification and Overexpression in Tumorigenesis.
| Autor: | Oliner JD; Jon Oliner Consulting, Garrett Park, Maryland 20896., Saiki AY; Oncology Research, Amgen, Thousand Oaks, California 91320., Caenepeel S; Oncology Research, Amgen, Thousand Oaks, California 91320. |
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| Jazyk: | angličtina |
| Zdroj: | Cold Spring Harbor perspectives in medicine [Cold Spring Harb Perspect Med] 2016 Jun 01; Vol. 6 (6). Date of Electronic Publication: 2016 Jun 01. |
| DOI: | 10.1101/cshperspect.a026336 |
| Abstrakt: | Mouse double minute 2 (MDM2) is a critical negative regulator of the tumor suppressor p53, playing a key role in controlling its transcriptional activity, protein stability, and nuclear localization. MDM2 expression is up-regulated in numerous cancers, resulting in a loss of p53-dependent activities, such as apoptosis and cell-cycle arrest. Genetic amplification and inheritance of MDM2 promoter single-nucleotide polymorphisms (SNPs) are the two best-studied mechanisms for up-regulating MDM2 activity. This article provides an overview of these events in human cancer, highlighting the frequent occurrence of MDM2 amplification in sarcoma and the role of SNP309 and SNP285 in regulating MDM2 expression and cancer risk. The availability of large-scale genomic profiling datasets, like those from The Cancer Genome Atlas Research Network, have provided the opportunity to evaluate the consequences of MDM2 amplification and SNP inheritance across high-quality tumor samples from diverse cancer indications. (Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.) |
| Databáze: | MEDLINE |
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