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. Author manuscript; available in PMC: 2021 Apr 22.
Published in final edited form as: Sci Transl Med. 2018 Jun 20;10(446):eaao2301. doi: 10.1126/scitranslmed.aao2301

Fig. 2. Genetic EGFR ablation in K-RAS mutated lung AC reduces tumor growth.

Fig. 2

(A) and (B) Kaplan-Meier analysis of K (K-rasG12D, n=24), KE (K-rasG12D:EgfrΔLep/ΔLep, n=28), KP (K-rasG12D:p53ΔLep/ΔLep, n=20) and KPE (K-rasG12D:p53ΔLep/ΔLep:EgfrΔLep/ΔLep, n=27) mice following intranasal infection with Ad.Cre. (C) Survival analysis of immunocompetent recipient mice following orthotopic transplantation of syngeneic K-ras G12D mutated and p53 deficient KP cells, with and without Egfr deletion (n=7 per group). (A) – (C) The median survival times of the respective groups are indicated. Differences in survival of groups were tested using the Log-rank test, and respective p values are shown. (D) Representative pictures of H&E staining including higher magnification of indicated area (bottom) of tumor bearing lungs 10 weeks post Ad.Cre inhalation of mice with specified genotypes. For quantitation, the mean values of two sections per mouse were used. Graphs represent mean of ratios ± s.d. of tumor area versus healthy lung area and mean of tumor numbers ± s.d. per section (n=13 mice for K-rasG12D and n=14 mice for K-rasG12D:EgfrΔLep/ΔLep). (E) Representative pictures of immunohistochemical staining of mouse lungs 10 weeks post tumor induction using antibodies specific for Ki67 and pErk. Tumor cell intrinsic expression of the respective genes in at least 5 individual tumors per mouse was evaluated using TissueGnostics software. Graphs represent mean ± s.d. of Ki67 and pErk positive tumor cells normalized to all tumor cells (n=5-7 mice per group). (F) Cell count of p53 deficient versus p53/EGFR double knockout A549 cells following standard in vitro cultivation. Graph represents mean ± s.d. of three individual clones per group. (G) Mean volumes ± s.d. of xenografted tumors comparing EGFR expressing versus EGFR deficient p53 knockout A549 cells, monitored over the course of the experiment as well as the endpoint tumor weight ± s.d. (n=6 per group). Picture illustrates the tumors after finalization of the experiment. (D) to (G) *p<0.05, ***p<0.001.