Document Detail


A role for Jag2 in promoting uveal melanoma dissemination and growth.
MedLine Citation:
PMID:  23211831     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Controlling the spread of uveal melanoma is key to improving survival of patients with this common intraocular malignancy. The Notch ligand Jag2 has been shown to be upregulated in primary tumors that metastasize, and we therefore investigated its role in promoting invasion and clonogenic growth of uveal melanoma cells.
METHODS: mRNA and protein expression of Notch pathway components were measured using qPCR and Western blot in uveal melanoma cell lines. Expression of Jag2 ligand was upregulated using Jag2-GFP-MSCV constructs or downregulated by sh-Jag2 in the uveal melanoma cell lines Mel285, Mel290, 92.1, and OMM1, and the effects on growth and invasion were assessed.
RESULTS: Jag2 was introduced into Mel285 and Mel290 cells, which have low baseline levels of both this ligand and Notch activity. Overall growth of the Jag2-expressing cultures increased somewhat, and a significant 3-fold increase in clonogenic growth in soft agar was also noted. Introduction of Jag2 increased motility in both wound-healing and transwell invasion assays. We also observed a significant increase in Jag2 and Hes1 mRNA in invasive OMM1 cells that had passed through a Matrigel-coated filter in the transwell assay when compared with noninvading cells. Loss-of-function studies performed in 92.1 and OMM1 lines using Jag2 shRNAs showed that downregulation of the ligand significantly suppressed cellular growth, invasion, and migration.
CONCLUSIONS: Our data suggest that Jag2 may play an important role in promoting Notch activity, growth, and metastasis in uveal melanoma.
Authors:
Laura Asnaghi; James T Handa; Shannath L Merbs; J William Harbour; Charles G Eberhart
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-10     Completed Date:  2013-03-12     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  295-306     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Blotting, Western
Cell Line, Tumor
Cell Movement
Homeodomain Proteins / genetics,  metabolism
Humans
Intercellular Signaling Peptides and Proteins / genetics,  metabolism*
Ligands
MAP Kinase Signaling System
Melanoma / metabolism,  pathology*
Membrane Proteins / genetics,  metabolism*
Neoplasm Invasiveness / pathology
Neoplasm Metastasis
Phosphorylation
RNA, Messenger / metabolism
Real-Time Polymerase Chain Reaction
Receptors, Notch / physiology*
Signal Transduction
Up-Regulation
Uveal Neoplasms / metabolism,  pathology*
Grant Support
ID/Acronym/Agency:
P30 EY001765/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Homeodomain Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/JAG2 protein, human; 0/Ligands; 0/Membrane Proteins; 0/RNA, Messenger; 0/Receptors, Notch; 149348-15-2/HES1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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