Contributed equally to the work.
Suppression of α5 gene expression is closely related to the tumorigenic properties of uveal melanoma cell lines
Article first published online: 15 JUN 2011
© 2011 John Wiley & Sons A/S
Pigment Cell & Melanoma Research
Volume 24, Issue 4, pages 643–655, August 2011
How to Cite
Landreville, S., Vigneault, F., Bergeron, M.-A., Leclerc, S., Gaudreault, M., Morcos, M., Mouriaux, F., Salesse, C. and Guérin, S. L. (2011), Suppression of α5 gene expression is closely related to the tumorigenic properties of uveal melanoma cell lines. Pigment Cell & Melanoma Research, 24: 643–655. doi: 10.1111/j.1755-148X.2011.00869.x
- Issue published online: 18 AUG 2011
- Article first published online: 15 JUN 2011
- Accepted manuscript online: 18 MAY 2011 11:59PM EST
- PUBLICATION DATA Received 7 March 2011, revised and accepted for publication 7 May 2011, published online 18 May 2011
- uveal melanoma;
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.