KRAS and lung adenoma: RUNX3, a lineage-determining transcription factor expressed in multiple tissues, is frequently downregulated in various tumors.45, 49 During lung development, RUNX3 has an essential role in terminal differentiation of lung epithelial cells: it is required for the generation of bronchiolar lineage cells and for the terminal differentiation of alveolar cells.45 Lee et al.48 found that RUNX3 is inactivated in nearly all human lung AAH and carcinogen-induced early mouse lung adenomas in which K-Ras is not yet mutated.