Fig. 1: p53 deficiency increases asparagine secretion to promote lymphoma proliferation.
a p53+/+ and p53−/− C57BL/6J mice injected i.v. with 5 × 105 EL4-Luc-GFP cells were treated i.p. with vehicle or ASNase (2 U/g) every 3 days for 3 weeks. Whole-mouse bioluminescence analysis and representative images are shown. The colour scale represents the intensity of emitted luminescence. Each group included 9 mice. i.v., intravenously; i.p., intraperitoneally. b Flow cytometry analysis of the frequencies of EL4-Luc-GFP cells (GFP+) in peripheral blood in recipient mice as treated in a. Peripheral blood from mice without injection/treatment was used as a control. c p53+/+ and p53−/− C57BL/6J mice were treated as in a, plasma Asn levels were determined by LC-MS. d Linear regression analysis of the concentrations of mouse plasma Asn and the number of EL4-Luc-GFP (GFP+) cells in peripheral blood. n = 36 mice. e Kaplan–Meier survival curves of p53+/+ and p53−/− C57BL/6J mice treated as in a. Mice without EL4 injection/treatment were used as controls (n = 3). The significant differences among groups were determined by the log-rank (Mantel-Cox) test. f Proliferation of indicated cell lines cultured for 48 h in DMEM containing no or 0.1 mM Asn or cultured in p53+/+ or p53−/− HCT116 cell conditioned-medium (CM) as indicated. g Proliferation of cells cultured in DMEM containing 0, 0.1 or 1 mM glutamate (Glu) or aspartate (Asp) for 48 h. h Asparagine levels in culture medium from p53+/+ or p53−/− HCT116 cells at the indicated culture time points were measured. i The cultured medium from p53+/+ or p53−/− HCT116 cells cultured for 24 h was used for culturing EL4 cells with 0 or 2 IU/ml ASNase for another 48 h. Cell proliferation was measured. Data are mean ± s.d., unpaired two-tailed Student’s t-test, *p < 0.05, **p < 0.01, ***p < 0.001, NS not significant. Source data are provided as a Source Data file.
