Figure 6. Systemic deletion of Hk2 in the mouse is therapeutic for oncogenic KRas-driven NSCLC.

A. Immunoblot showing HK2 and HK1 protein expression in tissues isolated from either Hk2^f/f or Hk2^f/f;UBC^CreERT2 mice two weeks after final tamoxifen injection. B. Schematic illustration of the experiment described in C–H. C. Representative images of H&E staining of whole-mount lung sections prepared from either KRas^LA2-G12D;Hk2^f/f or KRas^LA2-G12D;Hk2^f/f;UBC^CreERT2 lungs, 12 weeks after injection of tamoxifen at 8 weeks of age. Individual tumors are indicated by arrows (scale bar 4mm). D. Percentage tumor burden as calculated from the H&E sections of tumor bearing lungs from either KRas^LA2-G12D;Hk2^f/f or KRas^LA2-G12D;Hk2^f/f;UBC^CreERT2 mice at 20 weeks of age and after injection of tamoxifen at 8 weeks of age (n=8 per group). E. Tumor numbers calculated from the H&E stained sections of tumor bearing lungs from either KRas^LA2-G12D;Hk2^f/f or KRas^LA2-G12D;Hk2^f/f;UBC^CreERT2 mice (n=8 per group). F. Size distribution of tumors developed in the lungs of either KRas^LA2-G12D;Hk2^f/f or KRas^LA2-G12D;Hk2^f/f;UBC^CreERT2 mice (n=6 per group). G. Immunoblot showing HK2 and HK1 protein levels in tumor lysates extracted at 20 weeks of age, and after tamoxifen injection at 8 weeks of age. Lanes 1–4- tumors were randomly selected for analysis; lanes 5,6 – tumor size < 0.025mm²; lanes 7–9- tumor size 0.3–0.05mm²; lanes 10–14-tumor size 0.05–0.025mm². H. Quantification of Ki67 staining of the same size groups of tumors derived from either KRas^LA2-G12D;Hk2^f/f or KRas^LA2-G12D;Hk2^f/f;UBC^CreERT2 mice. Data presented in Figs. D, E and H are expressed as the mean ± SEM. See also Fig. S4.