Agonist-free transformation of the glucocorticoid receptor in human B-lymphoma cells

Berg, J.D. van den; Smets, L. A.; Rooij, H. Van

doi:10.1016/0960-0760(95)00271-5

Cited by 5 publications

(2 citation statements)

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“…Ligand-free GC receptor activation in stressed cells may therefore be mainly a consequence of metabolic perturbations in dying cells. On the other hand, the heat-treated cells were fully intact at the time of receptor studies and agonist-free GC receptor activation has also been clearly demonstrated in essentially viable populations, eg biochemically in aggregated lymphoma cells 9 and functionally in non-lymphoid CHO cells transfected with GC-sensitive CAT reporter constructs. 8 The studies with H.2 variant cells provided more direct evidence that the GC receptor can be instrumental in some forms of stress-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Hormone-free receptor activation has also been recently demCorrespondence: LA Smets; Fax: 31 20 51 22 050 Received 29 July 1997; accepted 29 October 1997 onstrated in a more physiological context, ie during spontaneous aggregation of follicular lymphoma cells. 9 These various observations hint at the possibility that multiple physiological but non-hormonal signals could kill lymphoid cells by ligand-independent activation of the GC receptor, leading to apoptosis. The demonstration by Kiefer et al 10 that a functional GC receptor is required for cAMP-mediated apoptosis of T leukemia cells, attests to this idea.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of the glucocorticoid receptor in stress-induced apoptosis of leukemic cells

et al. 1998

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Glucocorticoid (GC) hormones induce apoptosis in lymphoid and leukemic cells by binding and activating cytosolic GC receptors. Because physiological stress often causes hormone-free GC receptor activation, we have investigated if stress-induced apoptosis of lymphoid cells is also mediated by the activation of the GC receptor pathway. In S49 T lymphoma cells, heat shock and deprivation of growth factors or nutrients caused nuclear translocation and loss of agonist binding capacity of GC receptors, similar to that in cells incubated with the glucocorticoid dexamethasone (DEX). In variant S49 H.2 cells, cross-resistance to DEX, temperature shocks and growth factor deprivation were associated with a higher threshold for hormone-dependent and -independent receptor activation in situ and with impaired in vitro activation of cytosolic receptors. Cross-resistance to DEX, low serum and heat shock was abrogated, however, by pharmacological sensitization of GC receptor activation with the drug meta-iodobenzylguanidine (MIBG). Sensitive S49 cells and resistant variants did not differ in the expression levels of the apoptosis-regulating genes bax, bad, bcl-X and bcl-2, the status of the p53 gene nor in a different requirement for the growth factors Il-2, IL-4 or IL-9. The results suggest that ligand-independent activation of the GC receptor is a central signalling and controlling event in some forms of stress-induced apoptosis, assigning a novel function to the GC receptor in the regulation of lymphoid and leukemic cell numbers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%