0 22 Glucocorticoid-induced glucocorticoid-induced JJ 23 27 cell cell NN 28 33 death death NN 34 42 requires require VBZ 43 56 autoinduction autoinduction NN 57 59 of of IN 60 74 glucocorticoid glucocorticoid NN 75 83 receptor receptor NN 84 94 expression expression NN 95 97 in in IN 98 103 human human JJ 104 112 leukemic leukemic JJ 113 114 T t NN 115 120 cells cell NNS 120 121 . . . 123 125 In in IN 126 134 contrast contrast NN 135 137 to to TO 138 141 the the DT 142 150 negative negative JJ 151 165 autoregulation autoregulation NN 166 168 of of IN 169 183 glucocorticoid glucocorticoid NN 184 192 receptor receptor NN 193 194 ( ( ( 194 196 GR GR NNP 196 197 ) ) ) 198 208 expression expression NN 209 213 seen see VBN 214 216 in in IN 217 221 most most JJS 222 227 cells cell NNS 228 231 and and CC 232 239 tissues tissue NNS 239 240 , , , 241 243 GR GR NNP 244 254 expression expression NN 255 257 is be VBZ 258 268 positively positively RB 269 282 autoregulated autoregulate VBN 283 285 in in IN 286 291 human human JJ 292 300 leukemic leukemic JJ 301 302 T t NN 303 308 cells cell NNS 309 312 and and CC 313 315 in in IN 316 321 other other JJ 322 327 cells cell NNS 328 337 sensitive sensitive JJ 338 340 to to TO 341 363 glucocorticoid-induced glucocorticoid-induced JJ 364 368 cell cell NN 369 374 death death NN 374 375 . . . 376 378 To to TO 379 388 determine determine VB 389 396 whether whether IN 397 405 positive positive JJ 406 420 autoregulation autoregulation NN 421 423 is be VBZ 424 425 a a DT 426 435 necessary necessary JJ 436 445 component component NN 446 448 of of IN 449 471 glucocorticoid-induced glucocorticoid-induced JJ 472 476 cell cell NN 477 482 death death NN 482 483 , , , 484 485 a a DT 486 495 wild-type wild-type JJ 496 498 GR gr NN 499 503 gene gene NN 504 509 under under IN 510 513 the the DT 514 521 control control NN 522 524 of of IN 525 526 a a DT 527 549 tetracycline-regulated tetracycline-regulated JJ 550 558 promoter promoter NN 559 562 was be VBD 563 569 stably stably RB 570 581 transfected transfecte VBN 582 586 into into IN 587 611 glucocorticoid-resistant glucocorticoid-resistant JJ 612 617 cells cell NNS 618 625 lacking lack VBG 626 636 endogenous endogenous JJ 637 647 functional functional JJ 648 656 receptor receptor NN 656 657 . . . 658 671 Transfectants transfectant NNS 672 677 grown grow VBN 678 680 in in IN 681 684 the the DT 685 693 presence presence NN 694 696 of of IN 697 709 tetracycline tetracycline NN 710 719 contained contain VBD 720 725 about about RB 726 732 15,000 15,000 CD 733 747 receptors/cell receptors/cell NNS 747 748 , , , 749 750 a a DT 751 756 value value NN 757 770 approximately approximately RB 771 776 equal equal JJ 777 779 to to TO 780 785 basal basal JJ 786 791 level level NN 792 794 GR gr NN 795 805 expression expression NN 806 808 in in IN 809 833 glucocorticoid-sensitive glucocorticoid-sensitive JJ 834 840 6TG1.1 6tg1.1 NN 841 846 cells cell NNS 847 853 before before IN 854 861 steroid steroid NN 862 871 treatment treatment NN 871 872 . . . 873 878 Under under IN 879 884 these these DT 885 895 conditions condition NNS 895 896 , , , 897 910 dexamethasone dexamethasone NN 911 914 had have VBD 915 916 a a DT 917 924 minimal minimal JJ 925 931 effect effect NN 932 934 on on IN 935 939 cell cell NN 940 946 growth growth NN 946 947 , , , 948 956 elicited elicit VBD 957 963 little little JJ 964 980 internucleosomal internucleosomal JJ 981 984 DNA dna NN 985 998 fragmentation fragmentation NN 998 999 , , , 1000 1003 and and CC 1004 1011 induced induce VBD 1012 1014 no no DT 1015 1019 cell cell NN 1020 1025 cycle cycle NN 1026 1038 perturbation perturbation NN 1038 1039 . . . 1040 1042 In in IN 1043 1046 the the DT 1047 1054 absence absence NN 1055 1057 of of IN 1058 1070 tetracycline tetracycline NN 1070 1071 , , , 1072 1074 GR GR NNP 1075 1079 mRNA mRNA NNP 1080 1083 and and CC 1084 1091 protein protein NN 1092 1102 expression expression NN 1103 1112 increased increase VBD 1113 1121 2-3-fold 2-3-fold RB 1121 1122 , , , 1123 1126 and and CC 1127 1132 cells cell NNS 1133 1142 expressed express VBD 1143 1149 48,000 48,000 CD 1150 1159 receptors receptor NNS 1159 1160 , , , 1161 1162 a a DT 1163 1168 level level NN 1169 1175 nearly nearly RB 1176 1186 equivalent equivalent JJ 1187 1189 to to TO 1190 1194 that that DT 1195 1202 present present JJ 1203 1205 in in IN 1206 1212 6TG1.1 6tg1.1 NN 1213 1218 cells cell NNS 1219 1224 after after IN 1225 1227 18 18 CD 1228 1229 h h NN 1230 1232 of of IN 1233 1246 autoinduction autoinduction NN 1246 1247 . . . 1248 1253 Under under IN 1254 1259 these these DT 1260 1270 conditions condition NNS 1270 1271 , , , 1272 1285 dexamethasone dexamethasone NN 1286 1294 markedly markedly RB 1295 1304 inhibited inhibit VBD 1305 1309 cell cell NN 1310 1316 growth growth NN 1316 1317 , , , 1318 1324 caused cause VBD 1325 1327 G1 g1 NN 1328 1334 arrest arrest NN 1334 1335 , , , 1336 1339 and and CC 1340 1347 induced induce VBD 1348 1359 significant significant JJ 1360 1376 internucleosomal internucleosomal JJ 1377 1380 DNA dna NN 1381 1394 fragmentation fragmentation NN 1394 1395 . . . 1396 1401 These these DT 1402 1409 studies study NNS 1410 1419 therefore therefore RB 1420 1427 suggest suggest VBP 1428 1432 that that IN 1433 1438 basal basal JJ 1439 1444 level level NN 1445 1447 GR gr NN 1448 1458 expression expression NN 1459 1461 is be VBZ 1462 1472 inadequate inadequate JJ 1473 1475 to to TO 1476 1483 mediate mediate VB 1484 1506 glucocorticoid-induced glucocorticoid-induced JJ 1507 1516 apoptosis apoptosis NN 1517 1519 in in IN 1520 1544 glucocorticoid-sensitive glucocorticoid-sensitive JJ 1545 1546 T t NN 1547 1552 cells cell NNS 1553 1556 and and CC 1557 1561 that that IN 1562 1570 positive positive JJ 1571 1585 autoregulation autoregulation NN 1586 1588 is be VBZ 1589 1590 a a DT 1591 1600 necessary necessary JJ 1601 1610 component component NN 1611 1613 of of IN 1614 1618 this this DT 1619 1626 process process NN 1626 1627 . . .