Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

Figure 6

In vivo lung alveoli and in vitro A549 model. (a) In vivo model. Bipotent progenitor cells differentiate into ATI cells and ATII cells. ATII cells have stem cell-like functions, which are able to differentiate into ATI cells by injury and to maintain themselves by self-renewal. When EGFR and/or K-RAS are mutated, they may cause transformation of ATII cells. (b) In vitro A549 model proposed from the current study. A549 has been demonstrated to have K-RAS mutation (G12S) and EGFR amplification. In A549 clones, B7 have characters of ATII cell, and H12 have characters of both ATI and ATII cells. Both B7 and H12 can be enhanced the cell-type-specific markers of ATII-like cells by treatment of U0126 + DCIK. Injury, TGF-β, and IGF-1 may regulate differentiation from ATII-like cells into ATI-like cells. Black arrow: direction of differentiation; red arrow: experimental stimuli; dotted arrow: hypothesis. Yellow oval: nuclei of normal cells; black oval: nuclei of cancer cells; gray oval: nuclei of differentiated clones.