SMAD3 and papilloma: In two chemical carcinogenesis studies using Smad3+/− and Smad3−/− mice, it was found that in contrast to Smad2 deletion, Smad3+/− mice developed fewer tumors compared to wild-type controls [68]; Smad3−/− mice also developed fewer papillomas than wildtype controls and did not progress to SCC [57].