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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Cancer Discov. 2013 Aug 21;3(11):10.1158/2159-8290.CD-13-0397. doi: 10.1158/2159-8290.CD-13-0397

Figure 3. Loss of p53 does not ablate the increased early tumorigenesis or life span extension of mice carrying Braf V600E/+; Atg7−/− tumors.

Figure 3

A. Western blot analysis of ATG7 expression, LC3-I to LC3-II conversion, and accumulation of p62 in tumor lysates from Trp53+/+; BrafV600E/+; Atg7+/+, Trp53+/+; BrafV600E/+; Atg7−/− and Trp53−/−; BrafV600E/+; Atg7+/+, Trp53−/−; BrafV600E/+; Atg7−/− 14 weeks post Cre. Numbers refer to individual mice.

B. Representative micro-CT images and 3D reconstructions of Trp53−/−; BrafV600E/+; Atg7+/+ and Trp53−/−; BrafV600E/+; Atg7−/− tumors at 3 and 5 weeks post Cre demonstrating increased tumor in the Trp53−/−; BrafV600E/+; Atg7−/− mice at early time points. Numbers refer to individual mice. Quantification of normal lung volume is shown at right.

C. Representative micro-CT images and 3D reconstructions of Trp53+/+; BrafV600E/+; Atg7+/+, Trp53+/+; BrafV600E/+; Atg7−/− and Trp53−/−; BrafV600E/+; Atg7+/+, Trp53−/−; BrafV600E/+; Atg7−/− tumors at 7 and 10 weeks post Cre demonstrating reduced tumor in the Trp53−/−; BrafV600E/+; Atg7−/− mice at late time points. Numbers refer to individual mice. Quantification of normal lung volume is shown at right.

D. Representative images of Ki67 staining of Trp53+/+; BrafV600E/+; Atg7+/+, Trp53+/+; BrafV600E/+; Atg7−/− and Trp53−/−; BrafV600E/+; Atg7+/+, Trp53−/−; BrafV600E/+; Atg7−/− tumors at 4 and 14 weeks post Cre. Scale bar= 10 μm Quantification is shown at right.

E. Kaplan Meier analysis of overall survival of Trp53+/+ and Trp53−/−; Braf V600E/+; Atg7+/+ and Braf V600E/+; Atg7−/− mice post Cre. Numbers of mice per group and median survival are indicated on graph. Note: this study was ended at 22 weeks once the p value was highly significant (p=0.0003).

F. Representative images of histology (H&E), Tom20 IHC, electron micrographs, and the enzymatic cytochrome c oxidase assay at the indicated time post Cre. For H&E, Scale bar=10 μm For Tom20, Scale bar= 2 μm. For EM, N=nucleus MT= mitochondria. Scale bar=500 nm. Arrows point to swollen mitochondria in Trp53−/−; Braf V600E/+; Atg7−/− tumors. For cytochrome c oxidase, arrows point to tumor regions, indicated by dashed lines, with defective mitochondria in the Trp53−/−; Braf V600E/+; Atg7−/− tumors. Scale bar =100 μm