‘Activation-labile’ glucocorticoid–receptor complexes of a steroid-resistant variant of CEM-C7 human lymphoid cells

Abstract

For cytoplasmic glucocorticoid–receptor complexes to enter and accumulate in the nucleus a temperature-dependent event, ‘activation’ is required^1–4. Activation can be achieved in vitro by increased ionic strength^3–6, dilution or gel filtration⁷ and is manifested by an increased affinity of steroid–receptor complex for DNA^3,5,7,8 and an altered elution profile from ion-exchange resins^9–11. Munck and Foley have shown¹² that activated complexes isolated from thymocytes elute from DEAE-cellulose in a manner identical to complexes activated in vitro. We report here that DEAE-cellulose chromatography of steroid–receptor complexes from CEM-C7, a cloned human leukaemic T-cell line sensitive to the cytolytic action of glucocorticoids^13–15, and its steroid-resistant subclone 4R4 demonstrated that steroid receptors of clone 4R4 cannot form stable activated complexes. This defines a new defect in receptor action, activation lability (r⁺act¹), which is unlike either the r⁻, r⁺nt⁻, or r⁺ntⁱ phenotypes previously described for mouse lymphoid variants^16–19.