Tamoxifen-inducible C/EBPs suppress growth of myeloid leukemias and 32Dc13 cells: DNA binding is requisite for the antiproliferative effects of C/EBPϵ but not C/EBPα. (A-C,E) Bone marrow of PML-RARα leukemic mice were harvested and transduced with retroviruses expressing C/EBPα-ER, C/EBPϵ-ER, or a mutant version of each that is deficient in DNA-binding activity (C/EBPαR289A-ER and C/EBPϵR211A-ER, respectively). Following 2 rounds of transduction, GFP-positive cells were sorted and injected into sublethally irradiated FVB/N females. After leukemias developed in recipient animals, 5 mice from each group were given either a placebo or 25 mg 4-HT. Animals that received C/EBPϵ-ER–transduced leukemias exhibited prolonged survival following treatment with 4-HT (mean survival time of 33 days compared with 26.4 days in the placebo group; P = .002). C/EBPϵR211A-ER had no effect on survival of leukemic mice (mean survival time of 37.4 days compared with 36.4 days in the placebo group). In animals receiving transplants with C/EBPα-ER– or C/EBPαR289A-ER–transduced leukemias, treatment with 4-HT significantly prolonged survival (P ≤ .003). Mean survival times for placebo and 4-HT–treated groups were 33.8 days and 46.4 days, respectively, for C/EBPα-ER mice and 31.4 days and 39.8 days, respectively, for C/EBPαR289A-ER mice. (D, F) 32Dcl3 cells were plated in 24-well dishes at 100 000 cells per well; transduced with retroviruses expressing C/EBPϵ-ER, C/EBPϵR211A-ER, C/EBPα-ER, or C/EBPαR289A-ER; and cultured in the absence or presence of 20 nM 4-HT. The growth curve represents the number of transduced cells at days 0, 2, 4, and 6. The results are mean ± SD from at least 3 independent experiments. (D) *P < .05 and (F) *P ≤ .01.