Fig. 1. Imposition of Myc hypomorphism in adult mice blocks progression of KRas^G12D-driven lung hyperplasia to adenocarcinoma.

a Schematic of study. Endogenous Myc was maintained at normal levels in MRK (Myc^TRE/TRE;β-actin-tTS^Kid/–;LSL-KRas^G12D/+) mice through development, neonatal growth and into adulthood (5 weeks old) by continuous administration of tetracycline. Endogenous Myc was then hypomorphed by withdrawal of tetracycline and three weeks later Adv-Cre administered by inhalation to trigger sporadic expression of KRas^G12D in lung epithelium. Mice were then euthanized 12, 22, or 32 weeks later. Control mice were treated identically save that tetracycline was maintained throughout. b Top left: percentage of tumour burden relative to total lung in non-hypomorphed (blue) versus hypomorphed (red) MRK mice at 12, 22, or 32 weeks post Adv-Cre activation of KRas^G12D. Results depict mean ± SD in each treatment group. The unpaired t-test with Welch’s correction was used to analyse tumour burden. *p < 0.05, **p < 0.01, ****p < 0.0001. SD = standard deviation. For 12 weeks: n = 6 for non-hypomorphed control and n = 8 for hypomorphed mice with p =  0.0115; for 22 weeks: n = 6 for non-hypomorphed control and n = 9 for hypomorphed mice with p < 0.0001; for 32 weeks: n = 6 for both non-hypomorphed control and hypomorphed mice with p = 0.0045. Top right: Representative H&E-stained sections of lungs from MRK mice at 32 weeks post Adv-Cre activation of KRas^G12D either non-hypomorphed (maintained on tetracycline) or hypomorphed (off tetracycline). Arrows mark regions shown at higher magnification below. Bottom left: Grading of tumours (after⁴³) in lungs from MRK mice at 32 weeks post Adv-Cre activation of KRas^G12D, either non-hypomorphed (control, maintained on tetracycline) or hypomorphed (off tetracycline). Results depict quantitation of total numbers of tumours of each grade, with the means indicated. Source data are provided as a Source Data file.