Growth-related Gene Expression in Type 2 Alveolar Epithelial Cells

Abstract

Our laboratory is studying mechanisms of growth control in alveolar type 2 cells. This highly differentiated cell is induced to proliferate in lungs of animals of all ages during various forms of growth and during the repair process after lung injury. Using type 2 (T2) cells isolated from adult and neonatal rat lungs and an SV40-T transfected T2 cell line, we have shown tha growth-arrested T2 cells constitutively express genes associated with G1 and S phase of the cell cycle, yet they do not efficiently translate the proteins encoded by these genes. This block of growth-related gene expression is post-transcriptional and appears to involve mechanisms that control translation, perhaps at the level of initiation. Furthermore, growth-arrested T2 cells initiate DNA synthesis; however, the cells do not complete the cell cycle, suggesting that they are arrested in a late stage, perhaps the G1/S border. Differential screening of a cDNA library of growth-arrested T2 cells with DNA from growing and growth-arrested T2 cells has identified four families of genes preferentially expressed in the growth-arrested cells. These genes, which are in the process of being characterized, may be responsible for the unusual type of growth arrest demonstrated by T2 cells.