A single common electrophoretic abnormality of glucocorticoid receptors in human leukemia cells

作者: CW Distelhorst , BM Benutto , RC Griffith

DOI: 10.1182/BLOOD.V66.3.679.679

关键词: CytosolPeripheral blood mononuclear cellEndocrinologyMolecular biologyGel electrophoresisCell cultureReceptorBiologyInternal medicineGlucocorticoid receptorProteolysisLeukemia

摘要: We determined the mol wt of glucocorticoid receptors in human leukemia cells order to detect receptor defects that might cause resistance. Glucocorticoid intact were affinity labeled with [3H]dexamethasone-21-mesylate and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Receptors normal peripheral blood mononuclear six cell lines had 97,000. Malignant from ten 25 patients contained electrophoretically abnormal having 55,000 addition size (Mr = 97,000). The abnormality was not restricted a particular type seen both newly diagnosed who received prior chemotherapy, including prednisone. generated when only assayed under conditions favor proteolysis or cytosol containing form mixed receptors. same as mutant mouse lymphoma lines, S49 143R 55R, which have nuclear transfer-increased phenotype This work describes for first time single common electrophoretic cells. Further investigation could lead an improved understanding mechanisms resistance well method predicting are likely be resistant therapy.

参考文章(33)
KEITH R. YAMAMOTO, MARTHA R. STAMPFER, ULRICH GEHRING, CAROL H. SIBLEY, Genetic approaches to steroid hormone action. Recent Progress in Hormone Research. ,vol. 32, pp. 3- 32 ,(1976) , 10.1016/B978-0-12-571132-6.50008-7
R Mastrangelo, R Malandrino, R Riccardi, P Longo, FO Ranelletti, S Iacobelli, Clinical implications of glucocorticoid receptor studies in childhood acute lymphoblastic leukemia Blood. ,vol. 56, pp. 1036- 1040 ,(1980) , 10.1182/BLOOD.V56.6.1036.1036
H.G. Dellweg, A. Hotz, K. Mugele, U. Gehring, Active domains in wild-type and mutant glucocorticoid receptors. The EMBO Journal. ,vol. 1, pp. 285- 289 ,(1982) , 10.1002/J.1460-2075.1982.TB01161.X
Gerald R. Crabtree, Allan Munck, Kendall A. Smith, Glucocorticoid Receptors and Sensitivity of Isolated Human Leukemia and Lymphoma Cells Cancer Research. ,vol. 38, pp. 4268- 4272 ,(1978)
S S Simons, R E Schleenbaker, H J Eisen, Activation of covalent affinity labeled glucocorticoid receptor-steroid complexes. Journal of Biological Chemistry. ,vol. 258, pp. 2229- 2238 ,(1983) , 10.1016/S0021-9258(18)32912-0
Mark E. Costlow, Ching-Hon Pui, Gary V. Dahl, Glucocorticoid receptors in childhood acute lymphocytic leukemia. Cancer Research. ,vol. 42, pp. 4801- 4806 ,(1982)
R McCaffrey, A Lillquist, R Bell, Abnormal Glucocorticoid Receptors in Acute Leukemia Cells Blood. ,vol. 59, pp. 393- 400 ,(1982) , 10.1182/BLOOD.V59.2.393.393
O. Wrange, J.A. Gustafsson, Separation of the hormone- and DNA-binding sites of the hepatic glucocorticoid receptor by means of proteolysis. Journal of Biological Chemistry. ,vol. 253, pp. 856- 865 ,(1978) , 10.1016/S0021-9258(17)38183-8
DJ Gruol, ES Kempner, S Bourgeois, None, Characterization of the glucocorticoid receptor. Comparison of wild type and variant receptors. Journal of Biological Chemistry. ,vol. 259, pp. 4833- 4839 ,(1984) , 10.1016/S0021-9258(17)42921-8