Glucocorticoid Receptors in Leukemias, Lymphomas and Myelomas of Young and Old

  • Javed Ashraf
  • E. Brad Thompson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 330)


Glucocorticoids are well-known for their strong suppressive influence on certain cells of the immune system. These pharmacologic effects have long been taken advantage of to suppress immune responses and to treat leukemia and lymphomas. In recent years, a great deal has been learned of the mechanisms by which glucocorticoids affect lymphoid and related cells, and this information now provides a basis for studying the varying susceptibility to glucocorticoid therapy of the leukemias, lymphomas and myelomas in young and older patients. Expression of glucocorticoid receptors themselves is sometimes used as one predictive variable (Bloomfield, 1984; Thompson et al., 1985; Iacobelli et al., 1987). In this brief overview, we will outline the general pattern of expression with age of these groups of malignancies, discuss the recently established principles of glucocorticoid action, and describe some of our own experience with glucocorticoid effects on certain malignant lymphoid cell lines in vitro.


Glucocorticoid Receptor Glutamine Synthetase Steroid Receptor Mouse Mammary Tumor Virus Thyroid Hormone Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Akerblom, I. E., Slater, E. P., Beato, M., Baxter, J. D. and Mellon, P. L. Negative regulation by glucocorticoids through interference with a cAMP responsive enhancer. Science 241:350–353 (1988).CrossRefPubMedGoogle Scholar
  2. Altschmied, J., Muller, M., Baniahmad, A., Steiner, E. and Renkawitz, R. Cooperative interaction of chicken lysozyme enhancer sub-domains partially overlapping with a steroid receptor binding site. Nucleic Acid Research 17:4975–4991 (1989).CrossRefGoogle Scholar
  3. Antakly, T., Thompson, E. B. and O’Donnell, D. Demonstration of the intracellular localization and up-regulation of glucocorticoid receptor by in situ hybridization and immunocytochemistry. Cancer Research 49:2230s–2234s (1989).PubMedGoogle Scholar
  4. Beato, M., Arnemann, J., Chalepakis, G., Slater, E. and Willmann, T. Gene regulation by steroid hormones. J. Steroid Biochem. 27:9–14 (1987).CrossRefPubMedGoogle Scholar
  5. Beato, M. Gene regulation by steroid hormones. Cell 56:335–344 (1989).CrossRefPubMedGoogle Scholar
  6. Beaulieu, S., Gagne, B. and Barden, N. Glucocorticoid regulation of proopiomelanocortin messenger ribonucleic acid control of rat hypothalamus. Mol. Endocrinol. 2:727–731 (1988).CrossRefPubMedGoogle Scholar
  7. Berczi, I. The influence of pituitary-adrenal axis on the immune system. In: Berczi, I. (ed.) Pituitaiy Function and Immunity. CRC Press Inc., Boca Raton, FL., pp. 54–134 (1986).Google Scholar
  8. Bloomfield, C. D. Glucocorticoid receptors in leukemia and lymphoma. J. Clin. Oncol., 2:323–328 (1984).PubMedGoogle Scholar
  9. Bronnegard, M., Andersson, O., Edwell, D., Lund, J., Norstedt, G. and Carlstedt-Duke, J. Human calpactin H (Lipocortin 1) messenger ribonucleic acid is not induced by glucocorticoid. Mol. Endocrinol. 2:732–739 (1988).CrossRefPubMedGoogle Scholar
  10. Buetti, E. and Diggelmann, H. Glucocorticoid regulation of mouse mammary tumor virus: identification of a short essential DNA region. EMBO J. 2:1423–1429 (1983).PubMedGoogle Scholar
  11. Burnstein, K. L. and Cidlowski, J. S. Regulation of gene expression by glucocorticoids. Ann. Rev. Physiol 51:683–699 (1989).CrossRefGoogle Scholar
  12. Camper, S.A., Yao, Y.A.S., and Rottman, F.M. Hormonal regulation of the bovine prolactin promoter in rat pituitary tumor cells. J. Biol. Chemistry 260:12246–12251 (1985).Google Scholar
  13. Carlstedt-Duke, J., Okret, S., Wrange, O. and Gustafsson, J-A. Immunochemical analysis of the glucocorticoid receptor: Identification of a third domain separate from the steroid-binding and DNA-binding domains. Proc. Natl. Acad. Sci. (USA). 79:4260–4264 (1988).CrossRefGoogle Scholar
  14. Carlstedt-Duke, J., Stromstedt, P. E., Wrange, O., Bergamn, T., Gustafsson, J-A. and Jornvall, H. Domain structure of the glucocorticoid receptor protein. Proc. Natl. Acad. Sci. (USA) 84:4437–4440 (1987).CrossRefGoogle Scholar
  15. Carlstedt-Duke, J., Stomstedt, P. E., Persson, B., Cederlund, E., Gustafsson, J-A. and Jornvall, H. Identification of hormone interacting amino acids residues with the steroid binding domain of the glucocorticoid receptor in relation to other steroid hormone receptors. J. Biol. Chem. 263:6842–6846 (1982).Google Scholar
  16. Carson-Jurica, M. A., Schrader, W. T. and O’Malley, B. W. Steroid receptor superfamily: Structure and functions. Endocrin. Rev. 11:201–220 (1990).CrossRefGoogle Scholar
  17. Cavanaugh, A. H., Gokal, P. K., Lawther, R. P. and Thompson E. A. Jr. Glucocorticoid inhibition of initiation of transcription of the DNA encoding rRNA (rDNA) in lymphosarcoma P1798 cells. Proc. Natl. Acad. Sci. (USA). 81:718–721 (1984).CrossRefGoogle Scholar
  18. Chalepakis, G., Arnemann, J., Slater, E., Bruller, H. J., Gross, B. and Beato, M. Differential genes activation by glucocorticoids and progestins through the hormone regulatory element of mouse mammary tumor virus, Cell. 53:371–382 (1988).CrossRefPubMedGoogle Scholar
  19. Charron J. and Drouin J. Glucocorticoid inhibition of transcription from episomal proopimelancortin gene promoter. Proc. Natl. Acad. Sci. USA. 83:8903–8907 1986Google Scholar
  20. Dalman, F. C., Bresnick, E. H., Patel, P. D., Perdew, G. H., Watson, J.J., Jr. and Pratt, W. B. Direct evidence that the glucocorticoid receptor binds to hsp 90 at or near the termination of receptor translation in vitro. J. Biol. Chem., 264:19815–19821 (1989).PubMedGoogle Scholar
  21. Danesch, U., Gloss, B., Schmid, W., Schutz, G., Schule R. and Renkawitz, R. Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated by two widely separated glucocorticoid responsive elements. EMBO J. 6:625–630 (1987).PubMedGoogle Scholar
  22. Danielsen, M., Northrop, J. P. and Ringold, G. M. The mouse glucocorticoid receptor: Mapping of functional domains by cloning, sequencing and expression of wild-type and mutant receptor proteins. EMBO J. 5:2513–2522(1986).PubMedGoogle Scholar
  23. Danielsen, M., Hinck, L. and Ringold, G. M. Two amino acids within the knuckle of the first zinc finger specify DNA response element activation by the glucocorticoid receptor. Cell 57:1131–1138 (1989).CrossRefPubMedGoogle Scholar
  24. Danison, S. H., Sands, A. and Tindall, D. J. A tyrosine aminotransferase glucocorticoid response element also mediates androgen enhancement of gene expression. Endocrinol. 124:1091–1093 (1989).CrossRefGoogle Scholar
  25. Denis, M., Gustafsson, J. A., Wikstrom, A.-C. Interaction of the Mr 90,000 heat shock protein with the steroid-binding domain of the glucocorticoid receptor. J. Biol. Chem. 263:18520–18523 (1988).PubMedGoogle Scholar
  26. Distelhorst, C. W. and Benitto, B. M. Glucocorticoid receptor content of T-lymophocytes: Evidence for heterogeneity. J. Immunol. 126:1630–1634 (1981).PubMedGoogle Scholar
  27. Dong, Y., Poellinger, L., Gustafsson, J-A. and Okret, S. Regulation of glucocorticoid receptor expression: evidence for transcriptional and postranslational mechanisms. Mol. Endocrinol. 2:1256–1264 (1988).CrossRefPubMedGoogle Scholar
  28. Drouin, J., Sun, Y. L. and Nemers, M. Glucocorticoid repression of proopiomelanocortin gene transcription. J. Steroid Biochem. 34:63–69 (1989).CrossRefPubMedGoogle Scholar
  29. Eberwine, J. H. and Roberts, J. L. Glucocorticoid regulation of proopiomelanocortin gene trnascription in the rat pituitary. J. Biol. Chem. 259:2166–2170 (1984).PubMedGoogle Scholar
  30. Eisen, L. P., Elsasser, M. S. and Harmon, J. M. Positive regulation of the glucocorticoid receptor in human T-cells sensitive to the cytolytic effects of glucocorticoids. J. Biol. Chem. 263:12044–12048 (1988).PubMedGoogle Scholar
  31. Eriksson, P. and Wrange, O. Protein-protein contacts in the glucocorticoid receptor homodimer influence its DNA binding properties. J. Biol. Chem. 265:3535–3542 (1990).PubMedGoogle Scholar
  32. Evans, R. M. The steroid and thyroid hormone receptor superfamily. Science 240:889–895 (1988).CrossRefPubMedGoogle Scholar
  33. Evans, R. M. Molecular characterization of the glucocorticoid receptor. Rec. Prog. Hormone Res. 45:1–22 (1989).Google Scholar
  34. Fawell, S. E., Lees, J. A., White, R. and Parker, M. G. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell 60:953–962 (1990).CrossRefPubMedGoogle Scholar
  35. Foley, G. E., Lazarus, H., Farber, S., Uzman, B. G., Boone, B. A. and McCarthy, R. E. Cancer 18:522–529 (1965).CrossRefPubMedGoogle Scholar
  36. Foon, K. A., Gale, R. P. and Todd, R. F. III Recent advances in the immunologic classification of leukemia. Semin. Hematol. 23:257–283 (1986).PubMedGoogle Scholar
  37. Francke, U. and Foellmer, B. E. The glucocorticoid receptor gene is in 5q-q32. Genomics 4:610–612 (1989).CrossRefPubMedGoogle Scholar
  38. Freedman, L. P., Luisi, B. F., Korszun, Z. R., Basavappa, R., Sigler, P. B. and Yamamoto, K. R. The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature 334:543–546 (1988).CrossRefPubMedGoogle Scholar
  39. Fuxe, K., Wikstrom, A. C., Okret, S., Agnati, L. F., Hartstrand, A., Yu, Z. Y., Grandholm, L., Zoli, M., Vale, W., Gustafsson, J. A. Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel-and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor. Endocrinol. 117:1803–1812 (1985).CrossRefGoogle Scholar
  40. Gessani, S., McCandless, S. and Baglioni, C. The glucocorticoid dexamethasone inhibits synthesis of interferon by decreasing the level of its mRNA. J. Biol. Chem. 263:7454–7457 (1988).PubMedGoogle Scholar
  41. Giguere, V., Hollenberg, S. M., Rosenfeld, M. G. and Evans, R. M. Functional domains of the human glucocorticoid receptor. Cell 46:645–652 (1986).CrossRefPubMedGoogle Scholar
  42. Giguere, V., Ong, E. S., Segui, P. and Evans, R. Identification of a receptor for the morphogen retinoic acid. Nature 330:624–629 (1987).CrossRefPubMedGoogle Scholar
  43. Glass, C. K., Holloway, J. M., Devary, O. V. and Rosenfeld, M. G. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Cell 54:313–323 (1988).CrossRefPubMedGoogle Scholar
  44. Godowski, P. J., Rusconi, S., Miesfeld, R. and Yamamoto, K. R. Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement. Nature 325:365–368 (1987).CrossRefPubMedGoogle Scholar
  45. Gomi, M., Moriwaki, K., Katagiri, S., Kurata, Y. and Thompson, E. B. Glucocorticoid effects on myeloma cells in culture: correlation of growth inhibition with induction of glucocorticoid receptor messenger RNA. Cancer Research 50:1873–1878 (1990).PubMedGoogle Scholar
  46. Grange, T., Roux, J., Rigaud, G. and Pictet, R. Two remote glucocorticoid responsive units interact cooperatively to promote glucocorticoid induction of rat tyrosine aminotransferase. Nucleic Acid Research 17:8695–8709 (1989).CrossRefGoogle Scholar
  47. Graupner, G., Wills, K. N., Tzukerman, M., Zhang, X. K. and Pfahl, M. Dual regulatory role for thyroid-hormone receptors allows control of retinoic acid receptor activity. Nature 340:653–656 (1989).CrossRefPubMedGoogle Scholar
  48. Green, S. and Chambon, P Oestradiol induction of a glucocorticoid-responsive gene by a chimeric receptor. Nature 325:75–81 (1987).CrossRefPubMedGoogle Scholar
  49. Green, S., Kumar, V., Theulaz, I., Wahli, W. and Chambon, P. The N-terminal DNA binding ‘zinc finger’ of the oestrogen and glucocorticoid receptors determines target genes specificity. EMBO J. 7:3037–3044 (1988).PubMedGoogle Scholar
  50. Gustafsson, J-A., Carlstedt-Duke, J., Stromstedt, P. E., Wikstrom, A. C., Denis, M., Okret, S. and Dong, Y. Structure function and regulation of the glucocorticoid receptor. Prog, in Clin. and Biol. Res. 322:65–80 (1990).Google Scholar
  51. Ham, J., Thompson, A., Neddham, M., Webb, P. and Parker, M. Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumor virus. Nucleic Acid Research 16:5263–5277 (1988).CrossRefGoogle Scholar
  52. Harbour, D. V., Chambon, P. and Thompson, E. B. Steroid mediated lysis of lymphoblasts requires the DNA binding region of the steroid hormone receptor. J. Steroid Biochem. 35:1–9 (1990).CrossRefPubMedGoogle Scholar
  53. Hard, T., Kellenbach, E., Boelens, R., Maleo, B. A., Dahlman, K., Freedman, L. P., Carlstedt-Duke, J., Yamamoto, K. R., Gustafsson, J.-A. and Kaptein, R. Solution structure of the glucocorticoid receptor DNA binding domain. Science 249:157–160 (1990).CrossRefPubMedGoogle Scholar
  54. Harmon, J. M., Norman, M. R., Fowlkes, B. J. and Thompson, E. B. Dexamethasone induces irreversible GI arrest and death of a human lymphoid cell line. J. Cell Physiol. 98:267–278 (1979).CrossRefPubMedGoogle Scholar
  55. Harmon, J. M. and Thompson, E. B. Isolation and characterization of dexamethasone-resistant mutants from human lymphoid cell line CEM-C7. Mol. Cell. Bio. 1:512–521 (1981).Google Scholar
  56. Harmon, J. M., Schmidt, T. J. and Thompson, E. B. Deacylcortivazol acts through glucocorticoid receptors. J. Steroid Biochem. 14:273–279 (1981).CrossRefPubMedGoogle Scholar
  57. Harmon, J. M. and Thompson, E. B. Glutamine synthetase induction by glucocorticoids in the glucocorticoid-sensitive human leukemic cell line CEM-C7. J. Cell Physiol 110:155–160 (1982).CrossRefPubMedGoogle Scholar
  58. Harmon, J. M., Schmidt, T. J. and Thompson, E. B. Molybdate-sensitive and molybdate-resistant activation-labile glucocorticoid receptor mutants of the human lymphoid cell line CEM-C7. J. Steroid Biochem. 21:227–236 (1984).CrossRefPubMedGoogle Scholar
  59. Harmon, J. M., Thompson, E. B. and Baione, K. A. Analysis of glucocorticoidresistant human leukemic cells by somatic cell hybridization. Cancer Research 45:1587–1593 (1985).PubMedGoogle Scholar
  60. Harmon, J. M., Elsasser, M. S., Eisen, L. P., Urda, L. A., Ashraf, J. and Thompson, E.B. Glucocorticoid receptor expression in ‘receptorless’ mutants isolated from the human leukemic cell line CEM-C7. Mol. Endocrinol. 3:734–743 (1989).CrossRefPubMedGoogle Scholar
  61. Hock, W., Martin, F., Jaggi, R. and Groner, B. Regulation of glucocorticoid receptor activity. J. Steroid Biochem. 34:71–78 (1989).CrossRefPubMedGoogle Scholar
  62. Hoeck, W. and Groner B. Hormone-dependent phosphorylation of the glucocorticoid receptor occurs mainly in the amino-terminal transactivation domain. J. Biol. Chem. 265:5403–5408 (1990).PubMedGoogle Scholar
  63. Hollenberg, S. M., Weinberger, C., Ong, E. S., Cerelli, G., Oro, A., Lebo, R., Thompson, E. B., Rosenfeld, M. G. and Evans, R.M. Primary structure and expression of functional human glucocorticoid receptor cDNA. Nature 318:635–641 (1985).CrossRefPubMedGoogle Scholar
  64. Hollenberg, S. M., Giguere, V., Segui, P. and Evans, R. M. Colocalization of DNA-binding and transcriptional activation fonctions in the human glucocorticoid receptor. Cell 49:39–46 (1987).CrossRefPubMedGoogle Scholar
  65. Hollenberg, S. M. and Evans, R. M. Multiple and cooperative transactivation domains of the human glucocorticoid receptor. Cell 55:899–906 (1988).CrossRefPubMedGoogle Scholar
  66. Hollenberg, S.M., Giguere, B., Evans, R. Identification of two regions of the human glucocorticoid receptor hormone binding domain that block activation. Cancer Research 49:2292s–2294s (1989).PubMedGoogle Scholar
  67. Homo-Delarche, F. Glucocorticoid receptors and steroid sensitivity in normal and neoplastic human lymphoid tissues: A review. Cancer Research 44:431–437 (1984).PubMedGoogle Scholar
  68. Housley, P. R., Sanchez, E. R., Westphal, H. M., Beato, M. and Pratt, W. B. The molybdate-stabilized L-cell glucocorticoid receptor isolated by affinity chroma-tography or with a monoclonal antibody is associated with a 90-92 kDa non-steroidbinding phosphoprotein. J. Biol. Chem. 260:13810–13817 (1985).PubMedGoogle Scholar
  69. Iacobelli, S., Marchetti, P., De-Rossi, G., Mandelli, F. and Gentiloni, N. Glucocorticoid receptors predict response to combination chemotherapy in patients with acute lymphoblastic leukemia. Oncology 44:13–16 (1987).CrossRefPubMedGoogle Scholar
  70. Jantzen, H. M., Strahle, U., Gloss, B., Stewart, F. B., Schmid, W. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine amino transferase gene. Cell 49:29–38 (1987).CrossRefPubMedGoogle Scholar
  71. Kalinyak, J. E., Dorin, R. L., Hoffman, A. R. and Perlman, A. J. Tissue-specific regulation of glucocorticoid receptor mRNA by dexamethasone. J. Biol. Chem. 262:10441–10444 (1987).PubMedGoogle Scholar
  72. King, W. J. and Greene, G. L. Monoclonal antibodies localize estrogen receptor in the nuclei of target cells. Nature 307:745–747 (1984).CrossRefPubMedGoogle Scholar
  73. Klock, G., Strahle, U. and Schutz, G. Oestrogen and glucocorticoid responsive elements are closely related but distinct. Nature 329:734–736 (1987).CrossRefPubMedGoogle Scholar
  74. Kumar, V., Green, S., Staub, A. and Chambon, P. Localization of the oestradiol-binding and putative DNA binding domains of the human oestrogen receptor. EMBO J. 5:2231–2236 (1986).PubMedGoogle Scholar
  75. Lee, S. L., Stewart, K. and Goodman, R. H. Structure of the gene encoding rat thyrotripin releasing hormone. J. Biol. Chem. 263:16604–16609 (1988).PubMedGoogle Scholar
  76. Makinodan, T. and Hirayama, R. Age related change in immunologic and hormonal activities. IARC Sci. Publ. 58:55–70 (1985).PubMedGoogle Scholar
  77. McDonnell, D. P., Mangelsdorf, D. J., Pike, J. W., Haussier, M. R. and O’Malley, B. W. Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science 235:1214 (1987).CrossRefPubMedGoogle Scholar
  78. Mendel, D. B., Bodwell, J. E., Gometchu, B., Harrison, R. W. and Munck, A. Molybdate-stabilized non-activated glucocorticoid receptor complexes contain a 90-kDa non-steroid-binding phosphoprotein that is lost on activation. J. Biol. Chem. 261:3758–3763 (1986).PubMedGoogle Scholar
  79. Mendel, D. B., Orti, E., Smith, L. I., Bodwell, J. and Munck, A. Evidence for a glucocorticoid receptor cycle and nuclear dephosphorylation of the steroid-binding protein. Prog. in Clin. and Biol. Res. 322:65–80 (1990).Google Scholar
  80. Miesfeld, R., Okret, S. Wikstrom, A.-C., Wrange, O., Gustafsson, J.A., Yamamoto, K. R. Characterization of a steroid hormone receptor gene and mRNA in wild-type and mutant cells. Nature 312:779–781 (1984).CrossRefPubMedGoogle Scholar
  81. Miesfeld, R., Rusconi, S., Godowski, P. J., Maler, B. A., Okret, S., Wikstrom, A-C., Gustafsson, J-A. and Yamamoto, K. R. Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA. Cell 46:389–399 (1986).CrossRefPubMedGoogle Scholar
  82. Miesfeld, R., Godwski, P. J., Maler, B. A. and Yomamoto, K. A. Glucocorticoid receptor mutants that define a small region sufficient for enhancer activation. Science 236:423–427 (1987).CrossRefPubMedGoogle Scholar
  83. Miesfeld, R. L. The structure and function of steroid receptor proteins. In: Fasman, G.D. (ed.) Critical Review in Biochemistiy and Molecular Biology. CRC Press, Baco Raton, FL, pp. 101–117 (1989).Google Scholar
  84. Miller, J., McLachlan, A. D. and Klug, A. Repetitive zinc-binding domains in the protein transcription factor III A from xenopus oocytes. EMBO J. 4:1609–1614 (1985).PubMedGoogle Scholar
  85. Munck, A., Guyre, P. M. and Holbrook, N. J. Physiological funcitons of glucocorticoid in stress and their relation to pharmacological actions. Endocrine Reviews 5:25–44 (1984).CrossRefPubMedGoogle Scholar
  86. Nordeen, S. K., Kuhnel, B., Lawler-Heavner, J., Baber, D. A. and Edwards, D. P. A quantitative comparison of dual control of a hormone response element by progestins and glucocorticoids in the same cell line. Mol. Endocrinol. 3:1270–1278 (1989).CrossRefPubMedGoogle Scholar
  87. Norman, M. R., Harmon, J. M. and Thompson, E. B. Use of a human lymphoid cell line to evaluate interactions between prednisolone and other chemotherapeutic agents. Cancer Research 38:4273–4278 (1978).PubMedGoogle Scholar
  88. Norman, M. R., Harmon, J. M. and Thompson, E. B. The use of human cell culture systems for studying the action of glucocorticoids in human lymphoblastic leukemias. In: Foltherby, K. and Pal, S. B. (eds.), Hormones in Normal And Abnormal Human Tissues. deGruyter, New York, pp. 437–474 (1981).Google Scholar
  89. Okret, S., Poellinger, L., Dong, Y. and Gustafsson, J-A. Down-regulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone. Proc. Natl. Acad. Sci. (USA). 83:5899–5903 (1986).CrossRefGoogle Scholar
  90. Payvar, F., DeFranco, D., Firestone, G. L., Edgar, B., Wrange, O., Okret, S., Gustafsson, J-A. and Yamamoto, K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell 35:381–392 (1983).CrossRefPubMedGoogle Scholar
  91. Perrot-Applanat, M., Logeat, F., Groyer-Picard, M. T., Milgrom, E. Immunocytochemical study with monoclonal antibodies to progesterone receptor in human breast tumors. Cancer Research 47:2652–2661 (1985).Google Scholar
  92. Petkovich, M., Brand, N. J., Krust, A. and Chambon, P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330:444–450 (1987).CrossRefPubMedGoogle Scholar
  93. Picard, D. and Yamamoto, K. R. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J. 6:3333–3340 (1987).PubMedGoogle Scholar
  94. Picard, D., Salser, S. J. and Yamamoto, K. R. A movable and regulatable inactivation function within the steroid binding domain of the glucocorticoid receptor. Cell 54:1073–1080 (1987).CrossRefGoogle Scholar
  95. Pratt, W. B., Sanrhnz, F. R., Bresnick, F. H., Meshinchi, S., Scherrer, L. C., Dalman, F. C. and Welsh, M. J. Interaction of the glucocorticoid receptor with the Mr 90,000 heat shock protein: An evolving model of ligand-mediated receptor transformation and translocation. Cancer Res. 49:2220s–2221s (1989).Google Scholar
  96. Pratt, W. B. Glucocorticoid receptor structure and the initial events in signal transduction. Prog. in Clin. and Biol. Res. 322:119–132 (1990).Google Scholar
  97. Ptashne, M. How eukaryotic transcriptional activators work. Nature 335:683–689 (1988).CrossRefPubMedGoogle Scholar
  98. Raghow, R., Gossage, D. and Kang, A. H. Pretranslational regulation of type 1 collagen fibronectin and a 50-kilodalton noncollagenous extracellular protein by dexamethasone in rat fibroblasts. J. Biol. Chem. 261:4677–4677 (1986).PubMedGoogle Scholar
  99. Riegel A. T., Aitken S. C., Martin, M. B. and Schoenberg, D. R. Posttranscriptional regulation of albumin gene expression in xenopus liver: evidence for an estrogen receptor-dependent mechanism. Mol. Endocrinol. 1:160–167 (1987).CrossRefPubMedGoogle Scholar
  100. Ringold, G. M. Steroid hormone regulation of gene expression. Ann. Rev. Pharmacol. Toxico. 25:529–566 (1985).CrossRefGoogle Scholar
  101. Rosewicz, S., McDonald, A. R., Maddox, B. A., Goldfine, I. D., Miesfeld, R. L. and Longsdon, C. D. Mechanism of glucocorticoid receptor down-regulation by glucocorticoid. J. Biol. Chem. 263:2581–2584 (1988).PubMedGoogle Scholar
  102. Rusconi, S. and Yamamoto, K. Functional dissection of glucocorticoid receptor. EMBO J. 6:1309–1315 (1987).PubMedGoogle Scholar
  103. Ryseck, R. P., MacDonald-Bravo, H., Mattei, M. G., Ruppert, S., and Bravo, R. Structure, mapping and expression of a growth factor inducible gene encoding a putative nuclear hormonal binding receptor. EMBO J. 8:3327–3335 (1989).PubMedGoogle Scholar
  104. Sakai, D. D., Helms, S., Carlstedt-Duke, J., Gustafsson, J-A., Rottman, F. and Yamamoto, K. R. Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene. Gene Dev. 2:1144–1154 (1988).CrossRefPubMedGoogle Scholar
  105. Sanchez, E. R., Meshinchi, S., Tienrungroj, W., Schlesinger, M. J., Toft, D. O. and Pratt, W. B. Relationship of the 90-kDa murine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor. J. Biol. Chem. 262:6986–6991 (1987).PubMedGoogle Scholar
  106. Sanchez, E. R., Faber, L. E., Hanzel, W. J. and Pratt, W. B. The 56-59 kilodalton protein identified in untransformed steroid receptor complex is a unique protein that exists in cytosol in a complex with both the 70 and 90 kilodalton heat shock proteins. Biochemistry 29:5145–5152 (1990).CrossRefPubMedGoogle Scholar
  107. Sap, J. Munoz, A., Damm, K., Goldberg, Y., Ghysdael, J., Leutz, A., Beug, H. and Vennstrom, B. The c-erb A protein is a high affinity receptor for thyroid hormone, Nature 324:635–640 (1986).CrossRefPubMedGoogle Scholar
  108. Scheidereit, C., Geisse, S., Westphal, H. M. and Beato, M. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumor virus. Nature 304:749–752 (1983).CrossRefPubMedGoogle Scholar
  109. Schlecte, J. A., Simons, S. S., Jr., Lewis, D. A. and Thompson, E. B. [3H]-cortivazol a unique high affinity ligand for the glucocorticoid receptor. Endocrinol. 117:1355–1362 (1985).CrossRefGoogle Scholar
  110. Schlecte, J. A. and Schmidt, T. J. Use of [3H]-cortivazol to characterize glucocorticoid receptors in a dexamethasone-resistant human leukemic cell line. J. Clin. Endocrinol. and Metabol. 64:441–446 (1987).CrossRefGoogle Scholar
  111. Schmidt, T. J. and Litwack, G. Activation of the glucocorticoid receptor complex, Physiol. Rev. 62:1131–1192 (1982).PubMedGoogle Scholar
  112. Schmid, W., Strahle, U., Schutz, G., Schmitt, J. and Stunnenberg, H. Glucocorticoid receptor binds cooperatively to adjacent recognition sites. EMBO J. 8:2257–2263 (1989).PubMedGoogle Scholar
  113. Schmidt, T.J., Harmon, J.M. and Thompson, E.B. Activation-labile glucocorticoidreceptor complexes of a steroid-resistant variant of CEM-C7 human lymphoid cells. Nature 286:507–510 (1980).CrossRefPubMedGoogle Scholar
  114. Schule, R., Muller, M., Kaltschmidt, C. and Renkawitz, R. Many transcription factors interact synergistically with steroid receptors. Science 242:1418–1420 (1988).CrossRefPubMedGoogle Scholar
  115. Simons, S. S., Jr. and Thompson, E. B. Dexamethasone-21-mesylate: An affinity label of glucocorticoid receptors from rat hepatoma tissue culture cells. Proc. Natl. Acad. Sci. (U.S.A) 78:3541–3545 (1981).CrossRefGoogle Scholar
  116. Simons, S. S., Jr., Pumphrey, J. G., Rudikoff, S. and Eisen, H. Identification of cysteine 656 as the amino acid of hepatoma tissue culture cell glucocorticoid receptors that is covalently labeled by dexamethasone-21-mesylate. J. Biol. Chem. 262:9676–9680 (1987).PubMedGoogle Scholar
  117. Slater, E. P., Rabenau, O., Karin, M., Baxter, J. D. and Beato, M. Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene. Mol. Cell. Biol. 5:2984–2992 (1985).PubMedGoogle Scholar
  118. Smith, L. I., Bodwell, J. E., Mendel, D. B., Ciardelli, T., North, W. G. and Munch, A. Identification of cysteine 644 as the covalent site of attachment of dexamethasone 21-mesylate to murine glucocorticoid receptors in WEH 1-7 cells, Biochemistry 27:3747–3753 (1988).CrossRefPubMedGoogle Scholar
  119. Soler, J., Baiget, M., Rubiol, E., Guanabens, C., Nunes, V., Estivill, X. and Bosch, M. A. Genotype study of T-receptors in the diagnosis and classification of leukemias and lymphomas. Med. Clin. (Barc.) 91:135–138 (1988).Google Scholar
  120. Strahle, U., Klock, G. and Schutz, G. A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression. Proc. Natl. Acad. Sci. (U.S.A.) 84:7871–7875 (1987).CrossRefGoogle Scholar
  121. Thompson, E. B., Yuh, Y. S., Ashraf, J., Gametchu, B., Johnson, B. H. and Harmon, J. M. Mechanisms of glucocorticoid function in human leukemic cells: Analysis of receptor gene mutants of the activation-labile type using the covalent affinity ligand dexamethasone mesylate. J. Steroid Biochem. 30:63–70 (1988).CrossRefPubMedGoogle Scholar
  122. Thompson, E. B., Srivastava, D. and Johnson, B. H. Interactions of phenylpyrazolo steroid cortivazol with glucocorticoid receptors in steroid-sensitive and resistant human leukemic cells. Cancer Research 49:2253s–2258s (1989).PubMedGoogle Scholar
  123. Tsai, S. Y., Tsai, M. J., O’Malley, B. W. Cooperative binding of steroid hormone receptors contributes to transcriptional synergism at target enhancer elements. Cell 57:443–448 (1989).CrossRefPubMedGoogle Scholar
  124. Tsai, S. Y., Srinivasan, G., Allan, G. F., Thompson, E. B., O’Malley, B. W., and Tsai, M. J. Recombinant human glucocorticoid receptor induces transcription of hormone response genes in vitro. J. Biol Chem. 265:17055–17061 (1990).PubMedGoogle Scholar
  125. Umesono, K. and Evans, R. M. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell 57:1139–1146 (1989).CrossRefPubMedGoogle Scholar
  126. Vacca, G., Martinotti, S., Screpanti, I., Maroder, M., Felli, M. P., Farina, A. R., Gismondi, A., Santoni, A., Frati, L. and Gulino, A. Transcriptional regulation of the interleukin 2 gene by glucocorticoid hormones. Role of steroid receptor and antigen-responsive 5’ flanking sequences. J. Biol. Chem. 265:8075–8080 (1990).PubMedGoogle Scholar
  127. von der Ahe, D., Janich, S., Scheidereit, G., Renkawitz, R., Schutz, G. and Beato, M. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoter. Nature 313:706709 (1985).Google Scholar
  128. Walters, M. Steroid hormone receptors and the nucleus. Endocr. Rev. 6:512–543 (1985).CrossRefPubMedGoogle Scholar
  129. Walters, M. A. and Milbrandt, J. The NGFI-Bgene, a transcriptionally inducible member of the steroid receptor gene superfamily: genomic structure and expression in rat brain after seizure induction. Mol. Cell. Biol. 9:4213–4219 (1989).Google Scholar
  130. Webster, N. J. G., Green, S., Jin, J. R. and Chambon, P. The hormone binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function. Cell 54:199–207 (1988).CrossRefPubMedGoogle Scholar
  131. Weinberger, C., Hollenberg, S. M., Rosenfeld, M. G. and Evans, R. M. Domain structure of human glucocorticoid receptor and its relationship to the v-erb A oncogene product. Nature 318:670–672 (1985).CrossRefPubMedGoogle Scholar
  132. Weinberger, C., Thompson, C. C., Ong, E. S., Lebo, R., Gruol, D. J. and Evans, R. M. The c-erb A gene encodes a thyroid hormone receptor. Nature 324:641–646 (1986).CrossRefPubMedGoogle Scholar
  133. Wu, K. C. and Phahl, M. Variable responsiveness of hormone-inducible hybrid genes in different cell lines. Mol. Endocrinol. 2:1294–1301 (1988).CrossRefPubMedGoogle Scholar
  134. Yamamoto, K. R. Steroid receptor transcription of specific gene and gene networks. Ann. Rev. Genet. 19:209–252 (1985).CrossRefPubMedGoogle Scholar
  135. Yuh, Y. S. and Thompson, E. B. Complementation between glucocorticoid receptor and lymphocytolyis in somatic cell hybrids of two glucocorticoid resistant human leukemic clonal cell lines. Somatic Cell and Mol. Genet. 13:33–45 (1987).CrossRefGoogle Scholar
  136. Yuh, Y. S. and Thompson, E. B. Glucocorticoid effect on oncogene/growth gene expression in human T-lymphoblastic leukemic cell line CCRF-CEM: Specific c-myc mRNA suppression by dexamethasone. J. Biol. Chem. 264:10904–10910 (1989).PubMedGoogle Scholar
  137. Zawydiwski, R., Harmon, J. M. and Thompson, E. B. Glucocorticoid-resistant human acute lymphoblastic leukemic cell line with functional receptor. Cancer Res. 43:3865–3873 (1983).PubMedGoogle Scholar
  138. Zong, J., Ashraf, J. and Thompson, E. B. The promoter and first, untranslated exon of the human glucocorticoid receptor gene are GC rich but lack concenus glucocorticoid response element sites. Mol. Cell. Biol. 10:5580–5585 (1990).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Javed Ashraf
    • 1
  • E. Brad Thompson
    • 1
  1. 1.Department of Human Biological Genetics and ChemistryUniversity of Texas Medical BranchGalvestonUSA

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