Figure 5. Pggt1b^fl/+K^LSLLC mice develop lung cancer and hepatic leukocyte infiltration, and Pggt1b deficiency ameliorates these phenotypes.

(A–K) H&E-stained sections of lung and liver. (A) Advanced adenoma in lung of a day 11 Pggt1b^fl/+K^LSLLC mouse. (B) Diffuse adenocarcinoma that obliterates the majority of alveolar spaces in lung of a day 20 Pggt1b^fl/+K^LSLLC mouse; inset shows Ki-67 immunostaining. (C) AAH lesions (arrows) in lung of a day 20 Pggt1b^fl/flK^LSLLC mouse. (D) Magnification of AAH lesion indicated by left arrow in C. (E) Papillary adenoma in lung of a day 98 Pggt1b^fl/flK^LSLLC mouse. (F) Magnification of E. (G) Normal lung of a day 11 control mouse. (H) Magnification of G. (I) Leukocyte infiltration in liver of a Pggt1b^fl/+K^LSLLC mouse; arrows indicate clusters of leukocytes. (J) Normal appearance of liver from a day 62 Pggt1b^fl/flK^LSLLC mouse. (K) Normal liver from a day 17 control mouse. Scale bars: 50 μm (A, inset in B, D, F, H, and I–K); 100 μm (B, C, E, and G). (L) Western blot showing high levels of nonprenylated RAP1 in lung tumors from Pggt1b^fl/flK^LSLLC mice (lanes 1–4) and Cre-adenovirus–treated Pggt1b^fl/fl fibroblasts (lane 13) and lower levels in lung tissue from Pggt1b^fl/flLC mice (lanes 9 and 10). Nonprenylated RAP1 was undetectable in lung tumors from Pggt1b^fl/+K^LSLLC mice (lanes 5–8), normal lung tissue of Pggt1b^fl/+LC mice (lane 11), β-gal–adenovirus–treated Pggt1b^fl/fl (lane 12) and Pggt1b^fl/+ (lane 14) fibroblasts, and Cre-adenovirus–treated Pggt1b^fl/+ fibroblasts (lane 15). Total ERK1/2 expression was analyzed on the same blot as a loading control. Protein extracts from an additional 4 tumors of Pggt1b^fl/flK^LSLLC mice and 2 tumors from Pggt1b^fl/+K^LSLLC mice were analyzed with similar results.