AGONIST-FREE TRANSFORMATION OF THE GLUCOCORTICOID RECEPTOR IN HUMAN B-LYMPHOMA CELLS

Nuclear translocation of activated glucocorticoid receptors (GRs) is a necessary step in the signal transduction by these GC hormones. Altho ugh in vitro activation of GRs can occur in the absence of a functiona l ligand, it is generally assumed that binding of a cognate hormone is required for activation of the intracellular GR. By indirect immunocy tochemistry and Western-blot analysis, it was found that, in spontaneo usly aggregated human lymphoma DoHH2 cells, hormone-free GRs are locat ed in the nucleus. Disruption of the aggregates redistributed GRs to a predominantly cytosolic location. Upon spontaneous re-aggregation the GR again became localized to the nucleus. Intracellular cross-linking of the heteromeric receptor complex was applied to investigate the pr otein composition of cytoplasmic and nuclear receptors. Untransformed, cytosolic GRs could be demonstrated by [H-3]dexamethasone binding cap acity and hsp90 co-immunoprecipitation, whereas absence of these chara cteristics suggested an activated conformation of the nuclear GRs. The se observations suggest that cell-cell interactions are capable of tra nsforming GRs in the absence of a ligand. Copyright (C) 1996 Elsevier Science Ltd.