Oncotarget

Priority Research Papers:

Tumorigenesis promotes Mdm4-S overexpression

Vinod Pant, Connie A. Larsson, Neeraj Aryal, Shunbin Xiong, M. James You, Alfonso Quintas-Cardama and Guillermina Lozano _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:25837-25847. https://doi.org/10.18632/oncotarget.15552

Metrics: PDF 820 views  |   HTML 1121 views  |   ?  


Abstract

Vinod Pant1, Connie A. Larsson1, Neeraj Aryal1, Shunbin Xiong1, M. James You2, Alfonso Quintas-Cardama3 and Guillermina Lozano1

1 Department of Genetics, M.D. Anderson Cancer Center, Houston, Texas, 77030, USA

2 Department of Hematopathology, M.D. Anderson Cancer Center, Houston, Texas, 77030, USA

3 Department of Leukemia, M.D. Anderson Cancer Center, Houston, Texas, 77030, USA

Correspondence to:

Guillermina Lozano, email:

Vinod Pant, email:

Keywords: splicing, Mdmx, Mdm4-S/Mdm4, CLL, transgenic mouse

Received: October 19, 2016 Accepted: February 06, 2017 Published: February 20, 2017

Abstract

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15552