TY - JOUR
T1 - Resistance and susceptibility of human uveal melanoma cells to TRAIL-induced apoptosis
AU - Li, Haochuan
AU - Niederkorn, Jerry Y.
AU - Neelam, Sudha
AU - Alizadeh, Hassan
PY - 2005/5
Y1 - 2005/5
N2 - 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. Upregulation 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.
AB - 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. Upregulation 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.
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U2 - 10.1001/archopht.123.5.654
DO - 10.1001/archopht.123.5.654
M3 - Article
C2 - 15883285
AN - SCOPUS:18444361800
SN - 0003-9950
VL - 123
SP - 654
EP - 661
JO - Archives of Ophthalmology
JF - Archives of Ophthalmology
IS - 5
ER -