Related Experiment Video
Updated: Nov 17, 2025
Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
Published on: December 31, 2014
MDMX/MDM4 is highly expressed and contributes to cell growth and survival in anaplastic large cell lymphoma
Vaios Sinatkas1, Konstantina Stathopoulou2, Ioanna Xagoraris2
1Department of Pathology, University of Crete, Medical School, Heraklion, Greece.
Abstract:
We hypothesized that murine double minute X (MDMX), a negative p53-regulator, may be involved in dysfunctional p53-signaling in anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive and ALK-negative, characterized frequently by non-mutated TP53 (wt-p53). By western blot analysis, MDMX was highly expressed in ALK + ALCL and expressed at variable levels in ALK- ALCL cell lines. By immunohistochemistry, high MDMX levels were observed more frequently in ALK + ALCL (36/46; 78%), compared with ALK- ALCL tumors (12/29; 41%) (p < .0018, Mann-Whitney-test). FISH analysis showed MDMX-amplification in 1 of 13 (8%) ALK- ALCL tumors, and low-level MDMX copy gains in 2 of 13 (15%) ALK- ALCL and 3 of 11 (27%) ALK + ALCL tumors. MDMX-pharmacologic inhibition or siRNA-mediated MDMX-silencing were associated with activated p53 signaling, growth inhibition and apoptotic cell death in wt-p53 ALCL cells, providing evidence that targeting MDMX may provide a new therapeutic approach for ALCL patients with wt-p53.
Insights
Murine double minute X (MDMX) is highly expressed in anaplastic large cell lymphoma (ALCL) and targeting it activates p53 signaling. Inhibiting MDMX offers a potential new therapy for ALCL patients with wild-type p53.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Anaplastic large cell lymphoma (ALCL) often exhibits dysfunctional p53 signaling despite non-mutated TP53 (wt-p53).
- Murine double minute X (MDMX) is a known negative regulator of p53.
Purpose of the Study:
- To investigate the role of MDMX in wt-p53 ALCL.
- To evaluate MDMX as a therapeutic target in ALCL.
Main Methods:
- Western blot and immunohistochemistry to assess MDMX expression in ALCL.
- Fluorescence in situ hybridization (FISH) to detect MDMX gene amplification.
- Pharmacologic inhibition and siRNA-mediated silencing of MDMX in ALCL cell lines.
Main Results:
- MDMX was highly expressed in ALK-positive ALCL and variably in ALK-negative ALCL.
- High MDMX levels were significantly more frequent in ALK-positive ALCL.
- MDMX inhibition or silencing activated p53 signaling, inhibited growth, and induced apoptosis in wt-p53 ALCL cells.
Conclusions:
- MDMX is frequently overexpressed in ALCL and contributes to p53 pathway dysfunction.
- Targeting MDMX represents a promising therapeutic strategy for wt-p53 ALCL patients.
Related Concept Videos
02:23Abnormal Proliferation
02:38Mitogens and the Cell Cycle