Fig. 1 - Supplemental 4

Synergy between the Ventx reprogramming factor and the KRASG12V oncogene induces tumors in zebrafish larvae. (A) Phosphorylated ERK (pERK) immunofluorescence at 6 days post-fertilization (dpf) in nonactivated larvae (Ctrl), in larvea in which only KRASG12V was activated (KR) and in larvae in which both KRASG12V and VENTX were activated globally (KR+VX). Notice in the last one the strong pERK activation in the hyperplasic abdominal outgrowth. The digestive tract is shown between the red arrows. (B) Confocal microscopy of KR+VX zebrafish larva at 6 dpf (ventrolateral view) displays the immunofluorescence of active pERK (in green and indicated by red arrowheads) in the abdomen of a DAPI labeled zebrafish larva. (C) Histopathological analysis by hematoxylin and eosin (H&E) staining of hyperplasic tissues in zebrafish larvae (6 dpf) upon activation of KRASG12V and Ventx (KR+VX) is compared with normal tissues (Ctrl). Larvae overexpressing KR+VX develop hyperplasic and dysplastic cancer-like features and tissue outgrowth in the gut/intestine (red arrow), pancreas (blue arrow), and liver. (D) Such cancer-like features specifically and exclusively reduce the survival rate to 20% 2 weeks after induction.