Related Experiment Videos
Functional gene expression analysis uncovers phenotypic switch in aggressive uveal melanomas.
Michael D Onken1, Justis P Ehlers, Lori A Worley
1Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cancer Research
|May 3, 2006
Summary
Uveal melanoma classification reveals aggressive tumors exhibit epithelial traits and down-regulated ID2. Loss of ID2 drives E-cadherin expression, promoting cell growth and potential metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Microarray gene expression profiling aids cancer classification.
- Uveal melanoma classification predicts metastatic risk.
- Class 1 (low risk) vs. Class 2 (high risk) tumors identified.
Purpose of the Study:
- Identify biological correlates of aggressive Class 2 uveal melanoma.
- Investigate the role of ID2 and E-cadherin in uveal melanoma progression.
Main Methods:
- Gene expression profiling analysis.
- Gene Ontology enrichment analysis.
- In vitro cell culture and in vivo mouse models.
Main Results:
- Class 2 tumors show down-regulated neural crest/melanocyte genes and up-regulated epithelial genes.
- Class 2 tumors display epithelial morphology, E-cadherin, and cell-cell adhesion.
- ID2 down-regulation in Class 2 tumors, recapitulated by Id2 elimination.
- ID2 inhibition of E-cadherin promoter activator leads to E-cadherin up-regulation and anchorage-independent growth.
Conclusions:
- ID2 and E-cadherin play critical roles in uveal melanoma progression.
- ID2 loss promotes an aggressive, metastatic phenotype via E-cadherin.
- Identified potential therapeutic targets for uveal melanoma.