Tight junction-associated signaling pathways modulate cell proliferation in uveal melanoma.

Jayagopal A, Yang JL, Haselton FR, Chang MS
Invest Ophthalmol Vis Sci. 2011 52 (1): 588-93

PMID: 20861479 · PMCID: PMC3053300 · DOI:10.1167/iovs.10-5746

PURPOSE - To investigate the role of tight junction (TJ)-associated signaling pathways in the proliferation of uveal melanoma.

METHODS - Human uveal melanoma cell lines overexpressing the TJ molecule blood vessel epicardial substance (Bves) were generated. The effects of Bves overexpression on TJ protein expression, cell proliferation, and cell cycle distribution were quantified. In addition, localization and transcription activity of the TJ-associated protein ZO-1-associated nucleic acid binding protein (ZONAB) were evaluated using immunofluorescence and bioluminescence reporter assays to study the involvement of Bves signaling in cell proliferation-associated pathways.

RESULTS - Bves overexpression in uveal melanoma cell lines resulted in increased expression of the TJ proteins occludin and ZO-1, reduced cell proliferation, and increased sequestration of ZONAB at TJs and reduced ZONAB transcriptional activity.

CONCLUSIONS - TJ proteins are present in uveal melanoma, and TJ-associated signaling pathways modulate cell signaling pathways relevant to proliferation in uveal melanoma.

MeSH Terms (22)

Blotting, Western CCAAT-Enhancer-Binding Proteins Cell Adhesion Molecules Cell Cycle Cell Line, Tumor Cell Proliferation Flow Cytometry Fluorescent Antibody Technique, Indirect Genetic Vectors Heat-Shock Proteins Humans Melanoma Membrane Proteins Muscle Proteins Occludin Phosphoproteins Signal Transduction Tight Junctions Transcription Factors Transfection Uveal Neoplasms Zonula Occludens-1 Protein

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