Glucocorticoid binding properties of mouse thymic lymphosarcoma cell populations selected for resistance to the cytolytic effects of glucocorticoids in vivo.
Thirteen independently derived murine thymic lymphosarcoma lines were assayed for various aspects of sensitivity to glucocorticoid-induced cytolysis. All tumor lines were sensitive to cytolysis, as evidenced by profound tumor regression after pharmacologic doses of cortisol. All tumor lines contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 55 and 88% of these presumptive receptor sites underwent nuclear translocation during a 30-minute incubation at 37 degrees C. Dissociation constants (Kd) for the dexamethasone-receptor complex were between 1.5 and 3.6 nM in all cases. Kd for the triamcinolone acetonide-receptor complex were determined for a few tumor lines and were between 0.5 and 0.9 nM. Cytolysis-resistant subpopulations were selected by prolonged glucocorticoid treatment of BALB/c pi mice bearing tumors from seven of the lymphosarcoma lines. All seven resistant subpopulations contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 57 and 80% of these presumptive receptor sites underwent nuclear translocation under standard assay conditions. No resistant variants exhibited significantly reduced dexamethasone binding or nuclear translocation properties.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism*; D005260:Female; D006854:Hydrocortisone / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000503:physiopathology; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000503:physiopathology*
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D006854:Hydrocortisone