Figure 4.

Interference with the formation of active SMAD complexes promotes squamous cell carcinogenesis. (a) Ectopic expression of SKI in clonal KrasG12D p53^KO cells (left panel) induces a shift toward squamous morphology (right panel). (b) Western blot analysis of clonal KrasG12D p53^KO cells transduced with vector alone or SKI-expressing retroviruses. (c, d) Western blot analysis of clonal premalignant KrasG12D p53^KO cells (c), or primary ADC#6 cells (d) incubated for 2 days in the presence of 1 μM TGF-beta receptor inhibitor SB431542. (e) Ectopic expression of SKI or DN TBR2 in premalignant KrasG12D p53^KO cells accelerates tumorigenesis in nude mice (2 × 10⁴ cells per injection site). (f) Ectopic expression of SKI in TBR2-positive ADC accelerates tumorigenesis in vivo. Latencies of tumor development were compared with TBR2-negative SCC control. (g) Kinetics of tumor growth in nude mice injected with vector- or SKI-transduced KrasG12D p53^KO lung epithelial cells (2 × 10⁴ cells per injection site)