Cdc42 confers immunoresistance by ERK-dependent up-regulation of Bcl-2. (A) Immunoblot analysis of extracts prepared from 3 cA2K^b-Cdc42 and 3 cA2K^b-control fibrosarcomas. Note that phosphoepitopes indicative of ERK activation are detectable in Cdc42-expressing tumors. (B) cA2K^b-control MEFs (left panel) and cA2K^b-Cdc42 MEFs (right panel) were pretreated with the MEK inhibitor PD98059 (10 μM for 2 hours) or vehicle, followed by coincubation with allo-A2 CTL. Clonogenic survival in 1 representative of at least 3 repetitions. (C) Growth of cA2K^b-control (■ □) and cA2K^b-Cdc42 (● ○) fibrosarcomas in NOD/SCID mice. Mice received daily intraperitoneal injections of PD98059 (● ■) or vehicle (○ □). The arrowhead indicates the time point of adoptive transfer of allogeneic C57BL/6-derived splenocytes. Mean values plus or minus SE of bidimensional tumor sizes of 5 mice per group are shown. Vehicle-treated cA2K^b-Cdc42 fibrosarcomas grew significantly faster than the other groups (P < .001, ANOVA; *P < .05, **P < .01, Tukey multiple comparison). (D) Immunblot analysis of extracts from cA2K^b-Cdc42 and cA2K^b-control fibrosarcomas derived from mice treated with PD98059 or vehicle. Note reduced ERK phosphorylation and decreased Cdc42-induced (brief exposure) as well as endogenous (long exposure) Bcl-2 expression following treatment with PD98059.