Moreover, the average number of papillomata per mouse in Lgr5-Pten-/--TNF-/-mice was much lower compared to that in Lgr5-Pten-/- mice (Figure 2D, Figure 7F), and TNF-/- mice did not develop papilloma when receiving the same DMBA /TPA treatment (Figure 7E-F). This evidence concerns the gene TNF and papilloma.