Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression
J. Clin. Invest. Kristina E. Hoot, et al. 118:2722 doi:10.1172/JCI33713 [Go to this article.]

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.