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ERM is expressed by alveolar epithelial cells in adult mouse lung and regulates caveolin‐1 transcription in mouse lung epithelial cell lines

We previously identified an Ets cis‐element in the mouse caveolin‐1 promoter that is selectively activated in lung epithelial (E10), but not lung endothelial murine lung endothelial cell line (MFLM‐4), cell lines and therefore appears important for differential, cell‐specific caveolin‐1 transcription. In the present study, we demonstrate that immunostaining of adult mouse lung detects the ETS protein Ets‐related molecule (ERM PEA3) in distal lung epithelium in alveolar type I and II cells, but not in bronchial epithelium or lung endothelial cells. We tested ERM and polyomavirus enhancer activator 3 (PEA3) for their ability to increase endogenous caveolin‐1 transcripts and to activate caveolin‐1 promoter fragments containing the −865 Ets cis‐element. Chromatin immunoprecipitation (ChIP) assays show that both ERM and PEA3 bind to the caveolin‐1 promoter in murine E10, but not MFLM‐4, cells. Normalized luciferase activities show that only ERM activates the caveolin‐1 promoter in E10 cells, but neither protein enhances promoter activity in MFLM‐4 cells. Mutation of the Ets site blocks ERM‐mediated promoter activation in E10 cells. Furthermore, overexpression of ERM increases the cellular content of caveolin‐1 mRNA and protein, in E10, but not MFLM‐4, cells. The effects of PEA3 on the cellular content of endogenous caveolin‐1 expression are variable. These results demonstrate that ERM is involved in caveolin‐1 regulation in a murine lung epithelial, but not lung endothelial cell line. We conclude that transcriptional regulation of caveolin‐1 differs markedly between lung epithelial and endothelial cell lines, perhaps explaining why the onset of caveolin‐1 expression differs in epithelial and endothelial cells during lung development. J. Cell. Biochem. 102: 13–27, 2007. © 2007 Wiley‐Liss, Inc.