Fig. 2: Heterozygous Pik3caH1047R expression increases esophageal tumorigenesis.
From: Organismal metabolism regulates the expansion of oncogenic PIK3CA mutant clones in normal esophagus
a, Protocol 1: Cre-Pik3caH1047R-YFP/wt mice were induced one or three times with Cre-inducing drugs (Methods) and treated with DEN for 8 weeks starting 4 weeks post-induction. Uninduced mice were used as controls. Tissues were collected before exceeding the permitted humane endpoint or at 1 year after DEN. b, Typical DEN-treated esophagus opened and flattened epithelial side up showing four tumors (yellow arrows). Scale bar, 2 mm. c, The number of macroscopic esophageal tumors in DEN-treated mice, uninduced or induced one or three times before DEN treatment. Two-tailed Mann–Whitney test versus uninduced (n = 33, 35 and 23 animals, respectively). The red lines indicate average values. d, Protocol 2. Cre-Pik3caH1047R-YFP/wt mice were treated with DEN for 8 weeks followed by Cre induction. A subgroup of animals was then treated with the tumor promoter sorafenib (SOR) for 6 weeks. Tissues were collected before exceeding the permitted humane endpoint (Methods) or 1 year post-DEN treatment. Control groups received all treatments but were uninduced. e,f, The number (e) and size (f) of macroscopic esophageal tumors. Two-tailed Mann–Whitney test (n = 33, 13, 7 and 13 mice, as they appear in the graph). The red lines indicate average values. g, The frequency of MMs for the indicated driver genes detected in human ESCCs from data collected from the TCGA and ICGC databases. Esophageal cancer (EC) driver genes were selected using the Intogen tool (https://www.intogen.org/search). Only driver genes with MM frequency >2% are shown.
