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Fig. 1 | Radiation Oncology

Fig. 1

From: Mutant KRAS associated malic enzyme 1 expression is a predictive marker for radiation therapy response in non-small cell lung cancer

Fig. 1

Mutant KRAS is associated with ME1 and GOT1 expression in NSCLC. a Model of mutant KRAS-reprogrammed glutamine utilization (red). GLS1 = glutaminase 1; GLUD1 = glutamate dehydrogenase 1; GOT2 = mitochondrial aspartate aminotransferase; ASP = aspartate; GOT1 = cytosolic aspartate aminotransferase; OAA = oxaloacetate; MDH1 = malate dehydrogenase 1; ME1 = malic enzyme 1; GSR = glutathione disulfide reductase. b When fed doxycycline, the mice develop lung tumors that are dependent on constitutive KRAS G12D expression [20]. Within 48 h of doxycycline withdrawal, KRAS G12D expression was extinguished and whole-genome gene expression analyses of lung tumors were performed. Consistent with mutant KRAS-driven reprogramming of glutamine metabolism, ME1 and GOT1 levels were up-regulated when KRAS G12D was induced vs 48 h extinction with doxycycline withdrawl. c KRAS G12D induction upregulated ME1 mRNA in mouse doxycycline inducible KRAS G12D embryonic fibroblasts derived from the transgenic mice. d mRNA expression of ME1 in mutant KRAS vs wild-type KRAS NSCLC cell lines. Mutant KRAS lines: A549, CALU6, NCIH1155, NCIH1373, NCIH1385, NCIH1573, NCIH2030, NCIH2122, NCIH2347, NCIH460 and NCIH647. Wild-type KRAS lines: CALU3, HCC2108, HCC2279, HCC2935, HCC4006, NCIH322, NCIH520, NCIH522, NCIH596, NCIH661 and NCIH838. e NSCLC cell line dependencies on ME1 based on ATARiS gene phenotype value assessed from Project Achilles. Black bars = mutant KRAS cell. White bars = wild-type KRAS cell. Mutant KRAS lines: A549, CALU1, CORL23, HCC44, NCIH1650, NCIH1792, NCIH2122, NCIH23 and NCIH441. Wild-type KRAS lines: HCC2814, HCC827, NCIH1299, NCIH1437, NCIH1975, NCIH661, NCIH838 and HCC827GR5. f-g Seven day clonogenic survival assay of H522 and HCC44 with RNAi knockdown of ME1. h ME1 western blot in H522; band at 64 kDa. All results were compared using Student’s t-tests as indicated. *p < 0.05; **p < 0.01; ***p < .001

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