Epidermal hyperplasia and tumor promotion after accelerated TPA treatment. (A) wt and Rage−/− mice were treated with acetone (co) or 10 nmol TPA three times every 48 or 24 h, respectively, on the shaved back skin. Shown are the percent totals of Ki67-positive keratinocytes of three skin specimens from each genotype that were measured and analyzed as described in Fig. 1 C. (B) Representative images of skin sections from mice treated as described in A that were analyzed for S100a8, S100a9, and Tnf-α protein expression by IHC (brown staining) and counterstained with hematoxylin. Bar, 20 μm. (C) wt and Rage−/− mice were subjected to a modified DMBA/TPA skin carcinogenesis protocol with TPA treatment every 24 h and were analyzed as described in Materials and methods.