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Suppression of α5 gene expression is closely related to the tumorigenic properties of uveal melanoma cell lines
Author(s) -
Landreville Solange,
Vigneault François,
Bergeron MarjorieAllison,
Leclerc Steeve,
Gaudreault Ma,
Morcos Mohib,
Mouriaux Frédéric,
Salesse Christian,
Guérin Sylvain L.
Publication year - 2011
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2011.00869.x
Subject(s) - melanoma , cancer research , biology , transcription factor , repressor , cell culture , gene expression , cancer cell , regulation of gene expression , carcinogenesis , microbiology and biotechnology , gene , cancer , genetics
Summary Cancer aggressiveness is related to the ability of cancer cells to escape the anchorage dependency toward the extracellular matrix, a process regulated by the integrin α5β1 and its ligand fibronectin. Here, we characterized the expression of the α5 gene in human uveal melanoma cell lines with distinct tumorigenic properties and investigated some of the mechanisms underlying the variations of their malignancy. Strong and weak expression of α5 was observed in cells with no (T108/T115) and high (T97/T98) tumorigenic properties, respectively. Expression and DNA binding of the transcription factors Sp1, activator protein 1 (AP‐1) (both acting as activators), and nuclear factor I (NFI) (a strong repressor) to the α5 promoter were demonstrated in all cell lines. A reduced expression of AP‐1 combined with a dramatic increase in NFI correlated with the suppression of α5 expression in T97 and T98 cells. Restoring α5 expression in T97 cells entirely abolished their tumorigenicity in immunodeficient mice. These uveal melanoma cell lines might therefore prove particularly useful as cellular models to investigate α5β1 function in the pathogenesis of invasive uveal melanoma.