Stromal deletion of Tgfbr2 promotes inflammation-induced DNA damage and loss of <i>p15 and p16</i>.

<p>(A) Tgfbr2^fspKO mice developed forestomach SCC with 100% penetrance (left panel, scale bar: 50 µm). Mice died within 7 weeks with a median survival of 38 days (Kaplan Meier survival curve, Log rank p<0.001) (right panel). (B) IHC of CD45+ leukocytes in forestomach tissues of Tgfbr2^fspKO and Tgfbr2^flox/flox mice from embryonic day 16 (E16) to 5 weeks. Scale bar: 50 µm. (C) Immunofluorescence staining of 8-oxo-dG of forestomach samples of Tgfbr2^fspKO and Tgfbr2^flox/flox mice from E16 to 5 weeks. Scale bar: 100 µm. (D) Western blot of γ-H2AX from protein samples of Tgfbr2^fspKO and Tgfbr2^flox/flox forestomach (n = 3 mice for each group) (left panel), with Immunofluorescence staining of γ-H2AX on the right panels. Scale bar: 100 µm. (E) Genomic PCR of p15 and p16 from epithelial and stromal cells laser-dissected from Tgfbr2^fspKO and Tgfbr2^flox/flox forestomach tissues. The input for genomic PCRs was normalized with β-actin. (F) Western blot of p15 and p16 in the epithelial layer of forestomach from Tgfbr2^fspKO (n = 6) and Tgfbr2^flox/flox mice (n = 4). (G) Western blot of time course studies of p15/p16 expression in the epithelial layer of forestomach, showing reduced expression of p15 and p16 from 4 week of age in the Tgfbr2^fspKO mice. Str: Stroma; Epi: epithelia.