Activated Notch signaling promotes proliferation of MM cells and can specifically be blocked by the γ-secretase inhibitor DAPT. (A) Proliferative responses of Notch-expressing MM, Hodgkin, and Burkitt lymphoma cells after activation by Jagged1. HtTA-jag10 cells were plated in microtiter wells. Plates were washed with DMEM without tetracycline for induction of Jagged1 after 24 hours. Controls were washed with tetracycline-containing medium. After 48 hours, HtTA-jag10 cells were irradiated (120 Gy) and cocultured with MM, Hodgkin, and Burkitt lymphoma cells. Triplicate samples were cultured for 24 hours at 37°C in the presence or absence of tetracycline. ³[H]-thymidine was added to each well for 20 hours before determination of radioisotope incorporation into DNA. The results are shown as the mean of ³[H]-thymidine incorporation (± SD) of 3 independent proliferation assays. (A) Counts of activated cells (presence of Jagged1; ▪) are given relative to counts of nonactivated cells (absence of Jagged1; □), which were set arbitrarily at 100% for each cell line. (B) Jagged1-stimulated cells treated either with the γ-secretase inhibitor DAPT (▪) or with DMSO (□) alone as control. Counts of DAPT-treated cells are given relative to counts of control treated cells, which were set arbitrarily at 100% for each cell line. ^*P < .05; n.s. indicates not significant using the Student t test.