Fig. 3.
Hh response augments the number of Gli1-expressing stromal cells in cerulein-enhanced oncogenesis. (A) Schema for cerulein studies. Four-week-old ICG or KICG were given six hourly doses of cerulein on days 0 and 1. On days 0 through day 8 mice were given either vehicle, vismodegib, or SAG21k. Pancreata were harvested on day 8, 4 h after the last dose of Hh pathway modulating agent. (B–D and H) ICG mice do not form PanIN lesions in the setting of cerulein-induced pancreatitis. In these animals, vismodegib does not alter significantly the number of Gli1+ cells. However, SAG21k increases the amount of Gli1+ cells by 180-fold (*P < 0.0001, n = 6). Error bars indicate SEM. (E–G and I) In contrast, PanIN lesions are induced in KICG mice, associated with an 81-fold increase in Gli1+ cells observed in vehicle-treated KICG mice compared with vehicle-treated ICG controls (**P = 0.0001, n = 6). Vismodegib resulted in a nonsignificant decrease in Gli1+ cells in KICG mice (Vismo vs. Veh in I, ***P = 0.063, n = 6) whereas SAG21k resulted in a prominent increase (SAG21k vs. Veh in I, ****P < 0.0001, n = 6). Error bars indicate SEM.