Fig. 8: The IKK2-TPL2-JNK pathway mediates proliferation of LMP1-expressing PTLD tumor cells.

a IKK inhibition blocks the JNK and canonical NF-κB pathways in PTLD. PTLD099 and PTLD880 cells isolated from two different PTLD tumor biopsies and LCL877 corresponding to PTLD880 were incubated with DMSO or 10 µM of ACHP for 3 h. Chemiluminescence signals of immunoblots using the indicated antibodies were quantified directly. Paired signals standardized to total protein levels of three biological replicates are shown. Chemiluminescence values (y-axes) are relative and do not allow for direct comparison between graphs. b TPL2 mediates JNK, but not canonical NF-κB, activity in PTLD cells. The experiment was performed as described in a, except that 10 µM of TPL2 inhibitor TC-S7006 was used. Paired signals standardized to total protein levels of three (PTLD099, LCL877) or four (PTLD880) biological replicates are shown. c ACHP blocks proliferation of PTLD tumor cells. Cells were incubated with or without DMSO, or in the presence of 10 µM of ACHP. At the indicated times, MTT assays were performed. d TPL2 is required for PTLD proliferation. MTT assays in the presence of 10 µM of TPL2-IH. c, d The data are mean values ± SD of three biological replicates. a, b Statistical analysis was performed with the ratio paired T-test (two-tailed). c, d Statistical analysis was performed with two-way ANOVA at alpha 0.05. a–d p-values: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001, n.s. not significant.