Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment. | ||||||||
|
Resistance and susceptibility of human uveal melanoma cells to TRAIL-induced apoptosis.Li H, Niederkorn JY, Neelam S, Alizadeh H Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9057, USA. OBJECTIVE: To evaluate the resistance and susceptibility of human uveal melanoma cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). METHODS: The sensitivity of 11 human uveal melanoma cell lines was analyzed by flow cytometry for the expression of TRAIL receptors and the antiapoptotic protein survivin. Caspase-8 and caspase-10 expression was also examined using reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: Only 4 melanoma cell lines were sensitive to TRAIL-induced apoptosis. Positive correlation was observed between resistance and expression of survivin. Up-regulation of survivin by gene transfer enhanced resistance to TRAIL-induced apoptosis, whereas transfection with survivin antisense rendered resistant melanoma cells susceptible to TRAIL-induced apoptosis. Survivin expression and susceptibility to TRAIL-induced apoptosis could also be manipulated by treatment with actinomycin D, which produced a 30% to 50% decrease in the expression of survivin (P < .01) and a 5- to-7-fold increase in TRAIL-induced apoptosis (P < .001). CONCLUSIONS: Resistance of uveal melanoma cells to TRAIL-induced apoptosis is regulated by antiapoptotic proteins such as survivin. CLINICAL RELEVANCE: Manipulation of apoptosis regulatory proteins, such as survivin, may have therapeutic applications in the management of uveal melanomas. Published 10 May 2005 in Arch Ophthalmol, 123(5): 654-61.
© 2004-2008 Melanoma Research Today. All Rights Reserved. |
| ||||||
