Rage^−/− mice are protected against DMBA/TPA-induced tumor development. (A) wt and Rage^−/− mice were subjected to the DMBA/TPA skin carcinogenesis protocol and were assessed and statistically analyzed as described in Materials and methods. The graphs display the number of tumor-bearing mice (left, incidence) and the mean number of tumors per mouse (right, multiplicity) at the indicated time points after DMBA treatment. (B) Representative macroscopic pictures (top) and bright-field microscopic views of hematoxylin-eosin–stained sections (bottom) of wt and Rage^−/− tumors. Bars: (top) 1 mm; (bottom) 200 μm. (C) The percent total of Ki67-labeled tumor cells of three tumors from each genotype was calculated as described in Materials and methods. (D) Representative pictures of wt and Rage^−/− tumor sections that were analyzed by TUNEL assay (top, red signal) and by indirect IF staining of phospho-p65 protein (bottom, red signal), as described in Materials and methods. Nuclear staining was done with H33342 (blue signal). Inset shows a higher magnification of phospho-p65 stained nuclei. Bar, 100 μm. (E) The percent total of phospho-p65–labeled tumor cells within three tumors from each genotype was calculated as described in Materials and methods. Error bars represent the SEM.