TGF-β signaling occurs not only in tumor cells but also in surrounding non-tumorigenic epithelial cells and the tumor stroma.17 We have shown recently that low SMAD7 in both tumor tissue and surrounding tissue correlates with worse patient outcome.7 Similarly, Smad7 levels in the present model varied, when comparing different tissue areas of the same animal, independent if Tg or KO genotypes were existent (Supplementary Figure S3), thus verifying our ‘leaky' model as a powerful tool to experimentally mimic human patient characteristics. This evidence concerns the gene SMAD7 and neoplasm.