Temperature dependence of glucocorticoid binding in sensitive and refractory murine leukaemia cells

Leukemia Research
J D van den BergM Janssen

Abstract

The validity of in vitro assays in predicting the susceptibility of leukaemic cells to glucocorticoid-mediated lysis was evaluated in a panel of six murine leukaemia cell lines. In this panel susceptibility to glucocorticoids ranged from highly sensitive to fully resistant. The panel was screened for specific 3H-dexamethasone binding in whole cells and for activation of cytosolic receptors in cell lysates. Specific binding of 3H-dexamethasone was strongly affected by the incubation temperature. In all cell lines, rapid and reversible changes were observed in the stability of agonist-receptor association with a transition temperature of 28 degrees C. Below this temperature, intracellular receptors were found to be in a stable-binding, high-affinity configuration, masking differences in receptor status among the various cell lines. When assayed at 37 degrees C, refractory and fully resistant cells revealed nonsaturating, low-affinity binding of steroid. Saturating, high-affinity binding was, however, restored in these cells by the drug meta-iodobenzylguanidine with concomitant sensitization to dexamethasone-induced lysis. Contrary to observations with intact cells, heat-induced agonist-receptor dissociation in cytosols caused irr...Continue Reading

References

Feb 10, 1989·Cell·M Beato
Jan 1, 1985·Leukemia Research·E G LevineC D Bloomfield
Mar 1, 1984·Molecular and Cellular Biology·M Danielsen, M R Stallcup

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Citations

Dec 7, 2002·Hematological Oncology·C S ChimY L Kwong
Oct 1, 1994·The Journal of Steroid Biochemistry and Molecular Biology·J D van den BergM M van den Elshout
Mar 22, 2003·British Journal of Haematology·Eric G HaarmanAnjo J P Veerman
Jan 1, 1996·Leukemia & Lymphoma·L A Smets, J D van den Berg
Oct 1, 2005·International Journal of Language & Communication Disorders·Joanne K FillinghamMatthew A Lambon Ralph

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