Source: Annual Congress 2003 - Molecular biology of chronic lung disease and lung cancer
Disease area: Airway diseases

Abstract

The glucocorticoid receptor (GR) controls cell proliferation and cell differentiation. The inactive GR is localised in the cytoplasma and upon ligand binding migrates into the nucleus were it recognised specific DNA sequences, the glucocorticoid response element, and functions as a transcription factor. The GR activates the cell cycle inhibitor p21^(Waf1/Cip1) mediating the steroid-dependent arrest of the cell cycle. In cultures of human lung fibroblasts we observed that cell density (differentiation) affects the compartmentalisation of the GR. In growing cells withdrawing of a mitogenic stimulus (serum) results in a ligand independent activation and accumulation of the GR in the nucleus, while in the presence of 10% serum the GR is located in the cytosol. In high density, contact inhibited cells the withdrawing of serum results in a time dependent increase of the GR in the nucleus. When incubated with serum (10%) the expression of the GR is greatly enhanced within 3 hours and its distribution is equal in the cytosol and the nucleus. The nuclear accumulation of the GR is closely followed by expression and activation of p21^(Waf1/Cip1). Our data indicates that the density of cells, and therefore differentiation, affects the cell compartmental distribution and activation of the GR. The subsequent activity of p21^(Waf1/Cip1) further indicates the pathway how cell density controls proliferation in non-transformed normal human lung fibroblasts. Our results raise the question of the signalling pathway underlying the side effects of glucocorticoids.

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Citations should be made in the following way:
Q. J. Yang, J. J. Rüdiger, M. Tamm, M. Roth (Basel, Switzerland). Cell differentiation controls the cellular distribution of the glucocorticoid receptor. Eur Respir J 2003; 22: Suppl. 45, 1501

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