Figure 2. Accelerated tumor formation and malignant conversion of skin carcinogenesis in K5.Smad2-knockout mice.
(A) Kinetics of tumor formation. Arrow indicates TPA withdrawal. The seemingly more rapid tumor regression after TPA withdrawal in Smad2+/– and Smad2–/– groups compared with Smad2+/+ is due to necessity of euthanizing mice with a higher tumor burden. P < 0.001 compared with K5.Smad2–/– or K5.Smad2+/– and Smad2+/+ (B) Kinetics of malignant conversion. Smad2+/– and Smad2–/– mice had higher rates of malignant conversion (P < 0.05 compared with Smad2+/+ mice). The total number of mice of each genotype was used as a denominator for all time points through the entire course of tumor kinetics in A and B. (C) Tumor pathology and keratin markers. H&E staining of K5.Smad2–/– tumors showed less differentiation compared with K5.Smad2+/+ tumors. Immunofluorescence staining revealed that at the same histological stage, Smad2+/+ papillomas (Paps) expressed K1 (green) in suprabasal layers, whereas K5.Smad2–/– papillomas expressed K8 (red) and almost lost K1 in suprabasal layers. The dotted lines delineate the basement membrane. At SCC stages, K5.Smad2–/– tumors developed spindle cell carcinomas (SPCCs) when K5.Smad2+/+ tumors were well-differentiated SCCs. Rectangles in the bottom 2 panels denote areas of transition from SCC to SPCC. Two of these regions are enlarged 4 times to illustrate this transition (top row, far right panels). Scale bars: 100 μm.