Fig. 5
From: In vivo reprogramming drives Kras-induced cancer development
p53 mutation results in rapid development of in vivo reprogramming-induced PDAC in Kras-mutated pancreas. a A schematic illustration of the genetic construct of Pdx1 ires-Cre, LSL-KrasG12D, LSL-p53R172H, Rosa LSL-rtTA3, Col1a1::tetO-OSKM-ires-mCherry (KPC-OSKM) mice to induce pancreas-specific Kras/p53 compound mutations and in vivo reprogramming. b Experimental protocol for Dox treatment in KPC-OSKM chimeric mice. c Representative images of the pancreas of C-OSKM, KC-OSKM, KPC-OSKM mice given Dox for 3 days, followed by Dox withdrawal for 1 week. Scale bars, 500 μm. d pERK and Sirius red staining of the pancreas in KPC-OSKM mice. Scale bars, 100 μm. e Quantification of the PDAC area in the pancreas of KC-OSKM and KPC-OSKM chimeric mice. The PDAC area/affected area is shown. A box-and-whisker plot of the PDAC area/affected area. Solid lines in each box indicate the median. Bottom and top of the box are lower and upper quartiles, respectively. Whiskers extend to ±1.5 interquartile range (IQR). Numbers in parentheses indicate the number of mice examined. **p < 0.01, Mann–Whiteney U-test. f A schematic illustration of the genetic construct of KC mouse with Dox-inducible mCherry, Ptf1a, and Mist1 alleles. g Ptf1a and Mist1 induction inhibit caerulein-induced PanIN formation and activation of ERK signaling, but mCherry expression does not. Transgenes are induced by Dox treatment starting at 24 h before caerulein treatment. Chimeric mice were sacrificed after 7 days of caerulein treatment. Despite the infiltration of inflammatory cells, PanIN formation and pERK staining are hardly detectable in KC-Ptf1a and KC-Mist1 chimeric mice. Scale bars, 100 μm. h Quantification of the pERK-positive area/mCherry-positive area in the pancreas of caerulein-treated KC-mCherry, KC-Ptf1a, and KC-Mist1 mice. A box-and-whisker plot of the pERK-positive area/mCherry-positive area. Solid lines in each box indicate the median. Bottom and top of the box are lower and upper quartiles, respectively. Whiskers extend to ±1.5 interquartile range (IQR). Numbers in parentheses indicate the number of mice examined. **p < 0.01, *p < 0.05, Mann–Whiteney U-test
