Priority Research Papers:
Tumorigenesis promotes Mdm4-S overexpression
PDF | HTML | How to cite
Metrics: PDF 1718 views | HTML 2147 views | ?
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
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.