This Article Full Text Full Text (PDF) All Versions of this Article: 147/11/5187    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, D. Articles by Mendelson, C. R. Search for Related Content PubMed PubMed Citation Articles by Liu, D. Articles by Mendelson, C. R.

Estrogen Related Receptor- Enhances Surfactant Protein-A Gene Expression in Fetal Lung Type II Cells

Departments of Biochemistry (D.L., C.R.M.) and Obstetrics and Gynecology (M.M.H., C.R.M.), The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9038; and Molecular Oncology Group (V.G.), McGill University Health Center, Montreal, Quebec, Canada H3A 1A1

Address all correspondence to: Carole R. Mendelson, Ph.D., Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038. E-mail: carole.mendelson{at}utsouthwestern.edu.

Surfactant protein-A (SP-A) gene expression is developmentally regulated in fetal lung type II cells in concert with surfactant glycerophospholipid synthesis. In studies using transfected type II cells, we characterized a nuclear receptor element (NRE_SP-A, 5'-TGACCTTA-3') at –242 bp in the 5'-flanking sequence of human SP-A2 (hSP-A) gene that is essential for basal and cAMP-induced expression. NRE_SP-A has high sequence similarity to the consensus binding site for estrogen-related receptor (ERR). In the present study, we observed that ERR and ERR, but not ERRß, were expressed in human fetal lung type II cells. In vitro transcribed/translated ERR and ERR bound to the NRE_SP-A; DNase I footprinting using bacterially expressed ERR revealed a single DNase I protected region that included NRE_SP-A. In transient transfection assays of COS-7 and primary cultures of lung type II cells, ERR acting through NRE_SP-A increased hSP-A promoter activity, whereas ERR had no effect. ERR overexpression in lung type II cells enhanced cAMP induction of endogenous hSP-A expression, whereas cotransfection of protein kinase A catalytic subunit enhanced ERR stimulation of hSP-A promoter activity in lung adenocarcinoma cells. Mice homozygous null for the ERR gene manifested decreased SP-A expression relative to wild-type and heterozygous littermates. The ERR-specific inverse agonist XCT790 inhibited cAMP induced hSP-A expression in human fetal lung type II cells in a concentration-dependent manner, suggesting a role of peroxisome proliferator-activated receptor- coactivator 1. These findings suggest that ERR acting through NRE_SP-A is an important mediator of hSP-A gene expression and its induction by cAMP.

This article has been cited by other articles:

				R. Rajhans, H. B. Nair, S. S. Nair, V. Cortez, K. Ikuko, N. B. Kirma, D. Zhou, A. E. Holden, D. W Brann, S. Chen, et al. Modulation of in Situ Estrogen Synthesis by Proline-, Glutamic Acid-, and Leucine-Rich Protein-1: Potential Estrogen Receptor Autocrine Signaling Loop in Breast Cancer Cells Mol. Endocrinol., March 1, 2008; 22(3): 649 - 664. [Abstract] [Full Text] [PDF]

				A. S. Kauffman, M. L. Gottsch, J. Roa, A. C. Byquist, A. Crown, D. K. Clifton, G. E. Hoffman, R. A. Steiner, and M. Tena-Sempere Sexual Differentiation of Kiss1 Gene Expression in the Brain of the Rat Endocrinology, April 1, 2007; 148(4): 1774 - 1783. [Abstract] [Full Text] [PDF]