0 11 Involvement involvement NN 12 14 of of IN 15 25 Egr-1/RelA Egr-1/RelA NNP 26 33 synergy synergy NN 34 36 in in IN 37 51 distinguishing distinguish VBG 52 53 T t NN 54 58 cell cell NN 59 69 activation activation NN 70 74 from from IN 75 80 tumor tumor NN 81 89 necrosis necrosis NN 90 110 factor-alpha-induced factor-alpha-induced JJ 111 119 NF-kappa NF-kappa NNP 120 122 B1 B1 NNP 123 136 transcription transcription NN 136 137 . . . 139 147 NF-kappa NF-kappa NNP 148 149 B B NNP 150 152 is be VBZ 153 155 an an DT 156 165 important important JJ 166 179 transcription transcription NN 180 186 factor factor NN 187 195 required require VBN 196 199 for for IN 200 201 T t NN 202 206 cell cell NN 207 220 proliferation proliferation NN 221 224 and and CC 225 230 other other JJ 231 244 immunological immunological JJ 245 254 functions function NNS 254 255 . . . 256 259 The the DT 260 268 NF-kappa NF-kappa NNP 269 271 B1 B1 NNP 272 276 gene gene NN 277 284 encodes encode VBZ 285 286 a a DT 287 293 105-kD 105-kd JJ 294 301 protein protein NN 302 306 that that WDT 307 309 is be VBZ 310 313 the the DT 314 323 precursor precursor NN 324 326 of of IN 327 330 the the DT 331 334 p50 p50 NN 335 344 component component NN 345 347 of of IN 348 356 NF-kappa NF-kappa NNP 357 359 B. B. NNP 360 370 Previously previously RB 370 371 , , , 372 374 we we PRP 375 378 and and CC 379 385 others other NNS 386 390 have have VBP 391 403 demonstrated demonstrate VBN 404 408 that that IN 409 417 NF-kappa NF-kappa NNP 418 419 B B NNP 420 429 regulates regulate VBZ 430 433 the the DT 434 442 NF-kappa NF-kappa NNP 443 445 B1 b1 NN 446 450 gene gene NN 450 451 . . . 452 454 In in IN 455 459 this this DT 460 470 manuscript manuscript NN 471 473 we we PRP 474 478 have have VBP 479 491 investigated investigate VBN 492 495 the the DT 496 505 molecular molecular JJ 506 516 mechanisms mechanism NNS 517 519 by by IN 520 525 which which WDT 526 527 T t NN 528 532 cell cell NN 533 538 lines line NNS 539 549 stimulated stimulate VBN 550 554 with with IN 555 562 phorbol phorbol NN 563 575 12-myristate 12-myristate NN 576 586 13-acetate 13-acetate NN 587 588 ( ( ( 588 591 PMA PMA NNP 591 592 ) ) ) 593 596 and and CC 597 613 phytohemagglutin phytohemagglutin NN 614 615 ( ( ( 615 618 PHA PHA NNP 618 619 ) ) ) 620 627 display display VBP 628 641 significantly significantly RB 642 648 higher high JJR 649 655 levels level NNS 656 658 of of IN 659 667 NF-kappa NF-kappa NNP 668 670 B1 B1 NNP 671 679 encoding encode VBG 680 691 transcripts transcript NNS 692 696 than than IN 697 702 cells cell NNS 703 713 stimulated stimulate VBN 714 718 with with IN 719 724 tumor tumor NN 725 733 necrosis necrosis NN 734 746 factor-alpha factor-alpha NN 746 747 , , , 748 755 despite despite IN 756 759 the the DT 760 764 fact fact NN 765 769 that that IN 770 774 both both DT 775 782 stimuli stimulus NNS 783 791 activate activate VBP 792 800 NF-kappa NF-kappa NNP 801 803 B. B. NNP 804 820 Characterization Characterization NNP 821 823 of of IN 824 827 the the DT 828 836 NF-kappa NF-kappa NNP 837 839 B1 B1 NNP 840 848 promoter promoter NN 849 859 identified identify VBD 860 862 an an DT 863 868 Egr-1 egr-1 NN 869 873 site site NN 874 879 which which WDT 880 883 was be VBD 884 889 found find VBN 890 892 to to TO 893 895 be be VB 896 905 essential essential JJ 906 909 for for IN 910 914 both both CC 915 918 the the DT 919 935 PMA/PHA-mediated pma/pha-mediated JJ 936 945 induction induction NN 946 948 as as RB 949 953 well well RB 954 956 as as IN 957 960 the the DT 961 972 synergistic synergistic JJ 973 983 activation activation NN 984 992 observed observe VBN 993 998 after after IN 999 1002 the the DT 1003 1013 expression expression NN 1014 1016 of of IN 1017 1020 the the DT 1021 1025 RelA RelA NNP 1026 1033 subunit subunit NN 1034 1036 of of IN 1037 1045 NF-kappa NF-kappa NNP 1046 1047 B B NNP 1048 1051 and and CC 1052 1057 Egr-1 Egr-1 NNP 1057 1058 . . . 1059 1070 Furthermore furthermore RB 1070 1071 , , , 1072 1077 Egr-1 egr-1 NN 1078 1087 induction induction NN 1088 1091 was be VBD 1092 1100 required require VBN 1101 1104 for for IN 1105 1115 endogenous endogenous JJ 1116 1124 NF-kappa NF-kappa NNP 1125 1127 B1 B1 NNP 1128 1132 gene gene NN 1133 1143 expression expression NN 1143 1144 , , , 1145 1150 since since IN 1151 1169 PMA/PHA-stimulated pma/pha-stimulated JJ 1170 1171 T t NN 1172 1176 cell cell NN 1177 1182 lines line NNS 1183 1193 expressing express VBG 1194 1203 antisense antisense JJ 1204 1209 Egr-1 Egr-1 NNP 1210 1213 RNA RNA NNP 1214 1218 were be VBD 1219 1228 inhibited inhibit VBN 1229 1231 in in IN 1232 1237 their their PRP$ 1238 1245 ability ability NN 1246 1248 to to TO 1249 1259 upregulate upregulate VB 1260 1268 NF-kappa NF-kappa NNP 1269 1271 B1 B1 NNP 1272 1285 transcription transcription NN 1285 1286 . . . 1287 1290 Our our PRP$ 1291 1298 studies study NNS 1299 1307 indicate indicate VBP 1308 1312 that that IN 1313 1328 transcriptional transcriptional JJ 1329 1336 synergy synergy NN 1337 1345 mediated mediate VBN 1346 1348 by by IN 1349 1359 activation activation NN 1360 1362 of of IN 1363 1367 both both CC 1368 1373 Egr-1 Egr-1 NNP 1374 1377 and and CC 1378 1386 NF-kappa NF-kappa NNP 1387 1388 B B NNP 1389 1392 may may MD 1393 1397 have have VB 1398 1407 important important JJ 1408 1421 ramifications ramification NNS 1422 1424 in in IN 1425 1426 T t NN 1427 1431 cell cell NN 1432 1443 development development NN 1444 1446 by by IN 1447 1459 upregulating upregulate VBG 1460 1468 NF-kappa NF-kappa NNP 1469 1471 B1 B1 NNP 1472 1476 gene gene NN 1477 1487 expression expression NN 1487 1488 . . .