Temporal/spatial expression of nuclear receptor coactivators in the mouse lung.

Our laboratory has previously demonstrated that retinoic acid nuclear receptor, thyroid transcription factor-1 (TTF-1), and nuclear receptor coactivators such as cAMP response element binding protein (CREB) binding protein (CBP)/p300 and steroid receptor coactivator-1 (SRC-1) form an enhanceosome on the 5'-enhancer region of the human surfactant protein B gene. Immunohistochemistry was ...
used to identify cells that coexpressed CBP/p300, SRC-1, retinoid X receptor, and TTF-1 in the developing and mature lung. CBP/p300 and SRC-1 were expressed in the adult mouse lung, CBP and p300 being present in both alveolar type I and type II epithelial cells and SRC-1 and TTF-1 being restricted to type II epithelial cells. CBP/p300, SRC-1, and TTF-1 were readily detected in the nuclei of developing respiratory epithelial tubules in fetal mice from embryonic days 10 to 18. CBP/p300 and SRC-1 were also detected in developing mesenchymal cells. These coactivators were coexpressed with TTF-1 and SP-B in human pulmonary adenocarcinoma cells (H441 cells) in vitro. Interaction assays with a two-hybrid reporter analysis demonstrated direct interactions among TTF-1, SRC-1, and CBP/p300 in H441 cells. These findings support a role for retinoic acid receptor and nuclear receptor coactivators in the regulation of SP-B gene expression in the respiratory epithelium.
Mesh Terms:
Adenocarcinoma, Bronchiolo-Alveolar, Animals, Cyclic AMP Response Element-Binding Protein, E1A-Associated p300 Protein, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Histone Acetyltransferases, Humans, Lung, Lung Neoplasms, Mice, Nuclear Proteins, Nuclear Receptor Coactivator 1, Proteolipids, Pulmonary Surfactants, Respiratory Mucosa, Trans-Activators, Transcription Factors, Tumor Cells, Cultured, Two-Hybrid System Techniques
Am. J. Physiol. Lung Cell Mol. Physiol.
Date: Dec. 01, 2000
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