0 10 Inhibition Inhibition NNP 11 13 of of IN 14 21 phorbol phorbol NN 22 35 ester-induced ester-induced JJ 36 45 monocytic monocytic JJ 46 61 differentiation differentiation NN 62 64 by by IN 65 78 dexamethasone dexamethasone NN 79 81 is be VBZ 82 92 associated associate VBN 93 97 with with IN 98 113 down-regulation down-regulation NN 114 116 of of IN 117 122 c-fos c-fos NN 123 126 and and CC 127 132 c-jun c-jun NN 133 134 ( ( ( 134 138 AP-1 ap-1 NN 138 139 ) ) ) 139 140 . . . 142 150 Previous previous JJ 151 158 studies study NNS 159 163 have have VBP 164 169 shown show VBN 170 174 that that IN 175 184 treatment treatment NN 185 187 of of IN 188 193 human human JJ 194 201 myeloid myeloid JJ 202 210 leukemia leukemia NN 211 216 cells cell NNS 217 221 with with IN 222 258 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate NNP 259 260 ( ( ( 260 263 TPA TPA NNP 263 264 ) ) ) 265 267 is be VBZ 268 278 associated associate VBN 279 283 with with IN 284 293 induction induction NN 294 296 of of IN 297 306 monocytic monocytic JJ 307 322 differentiation differentiation NN 323 326 and and CC 327 337 expression expression NN 338 340 of of IN 341 344 the the DT 345 350 c-jun c-jun NN 351 354 and and CC 355 360 c-fos c-fos NN 361 366 early early JJ 367 375 response response NN 376 381 genes gene NNS 381 382 . . . 383 386 The the DT 387 394 present present JJ 395 399 work work NN 400 412 demonstrates demonstrate VBZ 413 417 that that IN 418 421 the the DT 422 436 glucocorticoid glucocorticoid NN 437 450 dexamethasone dexamethasone NN 451 459 inhibits inhibit VBZ 460 471 TPA-induced tpa-induced JJ 472 481 increases increase NNS 482 484 in in IN 485 490 c-jun c-jun NN 491 494 and and CC 495 500 c-fos c-fos NN 501 505 mRNA mrna NN 506 512 levels level NNS 513 515 in in IN 516 521 U-937 u-937 NN 522 530 leukemia leukemia NN 531 536 cells cell NNS 536 537 . . . 538 543 These these DT 544 552 findings finding NNS 553 557 were be VBD 558 568 associated associate VBN 569 573 with with IN 574 575 a a DT 576 581 block block NN 582 584 in in IN 585 595 appearance appearance NN 596 598 of of IN 599 602 the the DT 603 612 monocytic monocytic JJ 613 622 phenotype phenotype NN 622 623 , , , 624 633 including include VBG 634 644 inhibition inhibition NN 645 647 of of IN 648 659 TPA-induced tpa-induced JJ 660 669 increases increase NNS 670 672 in in IN 673 678 lamin lamin NN 679 680 A A NNP 680 681 , , , 682 687 lamin lamin NN 688 689 C C NNP 689 690 , , , 691 694 and and CC 695 703 vimentin vimentin NN 704 715 transcripts transcript NNS 715 716 . . . 717 722 Other other JJ 723 730 studies study NNS 731 735 have have VBP 736 748 demonstrated demonstrate VBN 749 753 that that IN 754 765 TPA-induced tpa-induced JJ 766 775 monocytic monocytic JJ 776 791 differentiation differentiation NN 792 795 and and CC 796 806 expression expression NN 807 809 of of IN 810 813 the the DT 814 819 c-jun c-jun NN 820 823 and and CC 824 829 c-fos c-fos NN 830 835 genes gene NNS 836 838 in in IN 839 846 myeloid myeloid JJ 847 855 leukemia leukemia NN 856 861 cells cell NNS 862 865 are be VBP 866 875 regulated regulate VBN 876 878 by by IN 879 886 protein protein NN 887 893 kinase kinase NNP 894 895 C C NNP 896 897 ( ( ( 897 900 PKC PKC NNP 900 901 ) ) ) 901 902 . . . 903 906 The the DT 907 914 finding finding NN 915 919 that that IN 920 933 dexamethasone dexamethasone NN 934 937 has have VBZ 938 940 no no DT 941 947 effect effect NN 948 950 on on IN 951 962 TPA-induced tpa-induced JJ 963 973 activation activation NN 974 976 of of IN 977 980 PKC PKC NNP 981 989 suggests suggest VBZ 990 994 that that IN 995 999 this this DT 1000 1014 glucocorticoid glucocorticoid NN 1015 1023 inhibits inhibit VBZ 1024 1031 signals signal NNS 1032 1042 downstream downstream JJ 1043 1045 or or CC 1046 1054 parallel parallel JJ 1055 1057 to to TO 1058 1062 this this DT 1063 1069 enzyme enzyme NN 1069 1070 . . . 1071 1078 Nuclear nuclear JJ 1079 1085 run-on run-on JJ 1086 1092 assays assay NNS 1093 1104 demonstrate demonstrate VBP 1105 1109 that that IN 1109 1110 : : : 1111 1112 ( ( ( 1112 1113 1 1 LS 1113 1114 ) ) ) 1115 1124 induction induction NN 1125 1127 of of IN 1128 1133 c-jun c-jun NN 1134 1137 and and CC 1138 1143 c-fos c-fos NN 1144 1154 expression expression NN 1155 1157 by by IN 1158 1161 TPA TPA NNP 1162 1164 is be VBZ 1165 1174 regulated regulate VBN 1175 1177 by by IN 1178 1193 transcriptional transcriptional JJ 1194 1204 mechanisms mechanism NNS 1204 1205 , , , 1206 1207 ( ( ( 1207 1208 2 2 LS 1208 1209 ) ) ) 1210 1221 TPA-induced tpa-induced JJ 1222 1232 expression expression NN 1233 1235 of of IN 1236 1241 c-jun c-jun NN 1242 1245 and and CC 1246 1251 c-fos c-fos NN 1252 1256 does do VBZ 1257 1260 not not RB 1261 1268 require require VB 1269 1276 protein protein NN 1277 1286 synthesis synthesis NN 1286 1287 , , , 1288 1291 and and CC 1292 1293 ( ( ( 1293 1294 3 3 LS 1294 1295 ) ) ) 1296 1307 TPA-induced tpa-induced JJ 1308 1318 expression expression NN 1319 1321 of of IN 1322 1326 both both DT 1327 1332 genes gene NNS 1333 1335 is be VBZ 1336 1345 inhibited inhibit VBN 1346 1348 at at IN 1349 1352 the the DT 1353 1368 transcriptional transcriptional JJ 1369 1374 level level NN 1375 1377 by by IN 1378 1391 dexamethasone dexamethasone NN 1391 1392 . . . 1393 1395 To to TO 1396 1403 further further RB 1404 1410 define define VB 1411 1414 the the DT 1415 1422 effects effect NNS 1423 1425 of of IN 1426 1439 dexamethasone dexamethasone NN 1440 1442 at at IN 1443 1446 the the DT 1447 1456 molecular molecular JJ 1457 1462 level level NN 1462 1463 , , , 1464 1466 we we PRP 1467 1475 prepared prepare VBD 1476 1477 a a DT 1478 1484 series series NN 1485 1487 of of IN 1488 1495 deleted delete VBN 1496 1501 c-jun c-jun NN 1502 1510 promoter promoter NN 1511 1520 fragments fragment NNS 1521 1527 linked link VBN 1528 1530 to to TO 1531 1534 the the DT 1535 1550 chloramphenicol chloramphenicol NN 1551 1568 acetyltransferase acetyltransferase NN 1569 1570 ( ( ( 1570 1573 CAT CAT NNP 1573 1574 ) ) ) 1575 1579 gene gene NN 1579 1580 . . . 1581 1590 Increases increase NNS 1591 1593 in in IN 1594 1597 CAT CAT NNP 1598 1606 activity activity NN 1607 1613 during during IN 1614 1623 transient transient JJ 1624 1634 expression expression NN 1635 1637 of of IN 1638 1643 these these DT 1644 1654 constructs construct NNS 1655 1657 in in IN 1658 1669 TPA-treated tpa-treated JJ 1670 1675 U-937 u-937 NN 1676 1681 cells cell NNS 1682 1687 could could MD 1688 1690 be be VB 1691 1699 assigned assign VBN 1700 1702 to to TO 1703 1706 the the DT 1707 1713 region region NN 1714 1715 ( ( ( 1715 1718 -97 -97 CD 1719 1721 to to TO 1722 1725 -20 -20 CD 1725 1726 ) ) ) 1727 1729 of of IN 1730 1733 the the DT 1734 1742 promoter promoter NN 1743 1747 that that WDT 1748 1756 contains contain VBZ 1757 1760 the the DT 1761 1765 AP-1 ap-1 NN 1766 1773 binding binding NN 1774 1778 site site NN 1778 1779 . . . 1780 1784 This this DT 1785 1794 induction induction NN 1795 1797 of of IN 1798 1801 CAT CAT NNP 1802 1810 activity activity NN 1811 1814 was be VBD 1815 1824 sensitive sensitive JJ 1825 1827 to to TO 1828 1841 dexamethasone dexamethasone NN 1841 1842 . . . 1843 1848 These these DT 1849 1857 findings finding NNS 1858 1865 suggest suggest VBP 1866 1870 that that IN 1871 1884 dexamethasone dexamethasone NN 1885 1899 down-regulates down-regulate VBZ 1900 1911 TPA-induced tpa-induced JJ 1912 1925 transcription transcription NN 1926 1928 of of IN 1929 1932 the the DT 1933 1938 c-jun c-jun NN 1939 1943 gene gene NN 1944 1950 during during IN 1951 1960 monocytic monocytic JJ 1961 1976 differentiation differentiation NN 1977 1979 by by IN 1980 1990 inhibiting inhibit VBG 1991 2001 activation activation NN 2002 2004 of of IN 2005 2008 the the DT 2009 2013 AP-1 ap-1 NN 2014 2018 site site NN 2018 2019 . . .