;PMID: 9797369 ;source_file_1390.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..41] = [t:0..41] ;1)sentence:[e:46..108] = [t:46..108] ;2)section:[e:112..167] = [t:112..167] ;3)section:[e:171..305] = [t:171..305] ;4)sentence:[e:309..327] = [t:309..327] ;5)sentence:[e:328..484] = [t:328..484] ;6)sentence:[e:485..593] = [t:485..593] ;7)sentence:[e:594..602] = [t:594..602] ;8)sentence:[e:603..722] = [t:603..722] ;9)sentence:[e:723..880] = [t:723..880] ;10)sentence:[e:881..889] = [t:881..889] ;11)sentence:[e:890..1033] = [t:890..1033] ;12)sentence:[e:1034..1207] = [t:1034..1207] ;13)sentence:[e:1208..1437] = [t:1208..1437] ;14)sentence:[e:1438..1585] = [t:1438..1585] ;15)sentence:[e:1586..1598] = [t:1586..1598] ;16)sentence:[e:1599..1712] = [t:1599..1712] ;17)section:[e:1716..1760] = [t:1716..1760] ;section 0 Span:0..41 ;Gastroenterology 1998 Nov;115(5):1144-53 (SEC (FRAG (IN:[0..16] Gastroenterology) (CD:[18..22] 1998) (CD:[23..31] Nov;115-LRB-) (CD:[31..32] 5) (-RRB-:[32..33] -RRB-) (CD:[33..38] :1144) (IN:[38..39] -) (CD:[39..41] 53))) ;sentence 1 Span:46..108 ;Oncogenic ras induces gastrin gene expression in colon cancer. ;[56..59]:gene-rna:"ras" ;[68..75]:gene-generic:"gastrin" ;[95..107]:malignancy:"colon cancer" (SENT (S-HLN (NP-SBJ (JJ:[46..55] Oncogenic) (NN:[56..59] ras)) (VP (VBZ:[60..67] induces) (NP (NN:[68..75] gastrin) (NN:[76..80] gene) (NN:[81..91] expression)) (PP (IN:[92..94] in) (NP (NN:[95..100] colon) (NN:[101..107] cancer)))) (.:[107..108] .))) ;section 2 Span:112..167 ;Nakata H, Wang SL, Chung DC, Westwick JK, Tillotson LG. (SEC (FRAG (NNP:[112..118] Nakata) (NNP:[119..120] H) (,:[120..121] ,) (NNP:[122..126] Wang) (NNP:[127..129] SL) (NNP:[129..130] ,) (NNP:[131..136] Chung) (NNP:[137..139] DC) (,:[139..140] ,) (NNP:[141..149] Westwick) (NNP:[150..152] JK) (,:[152..153] ,) (NNP:[154..163] Tillotson) (NNP:[164..167] LG.))) ;section 3 Span:171..305 ;Division of Digestive Diseases and Nutrition, Department of Medicine, ;University of North Carolina, Chapel Hill, North Carolina, USA. (SEC (FRAG (NNP:[171..179] Division) (CD:[180..182] of) (NNP:[183..192] Digestive) (NNP:[193..201] Diseases) (CC:[202..205] and) (NNP:[206..215] Nutrition) (,:[215..216] ,) (NNP:[217..227] Department) (IN:[228..230] of) (NNP:[231..239] Medicine) (,:[239..240] ,) (NNP:[241..251] University) (IN:[253..255] of) (NNP:[256..261] North) (NNP:[262..270] Carolina) (,:[270..271] ,) (NNP:[272..278] Chapel) (NNP:[279..283] Hill) (,:[283..284] ,) (NNP:[285..290] North) (NNP:[291..299] Carolina) (,:[299..300] ,) (NNP:[301..304] USA) (.:[304..305] .))) ;sentence 4 Span:309..327 ;BACKGROUND & AIMS: (SENT (NP (NN:[309..319] BACKGROUND) (CC:[320..321] &) (NNS:[322..326] AIMS) (::[326..327] :))) ;sentence 5 Span:328..484 ;The expression of gastrin, as a tumor growth factor, is significantly ;increased in some colon cancers compared with the low levels found in normal ;mucosa. ;[346..353]:gene-protein:"gastrin" ;[360..379]:gene-protein:"tumor growth factor" ;[417..430]:malignancy:"colon cancers" (SENT (S (NP-SBJ-2 (NP (DT:[328..331] The) (NN:[332..342] expression)) (PP (IN:[343..345] of) (NP (NN:[346..353] gastrin))) (,:[353..354] ,) (PP (IN:[355..357] as) (NP (DT:[358..359] a) (NN:[360..365] tumor) (NN:[366..372] growth) (NN:[373..379] factor)))) (,:[379..380] ,) (VP (VBZ:[381..383] is) (ADVP (RB:[385..398] significantly)) (VP (VBN:[399..408] increased) (NP-2 (-NONE-:[408..408] *)) (PP (IN:[409..411] in) (NP (DT:[412..416] some) (NN:[417..422] colon) (NNS:[423..430] cancers))) (S-ADV (NP-SBJ-1 (-NONE-:[430..430] *)) (VP (VBN:[431..439] compared) (NP-1 (-NONE-:[439..439] *)) (PP-CLR (IN:[440..444] with) (NP (NP (DT:[445..448] the) (JJ:[449..452] low) (NNS:[453..459] levels)) (VP (VBN:[460..465] found) (NP (-NONE-:[465..465] *)) (PP (IN:[467..469] in) (NP (JJ:[470..476] normal) (NN:[477..483] mucosa)))))))))) (.:[483..484] .))) ;sentence 6 Span:485..593 ;The aim of this study was to elucidate the transcriptional mechanisms of ;gastrin induction in colon cancer. ;[559..566]:gene-generic:"gastrin" ;[580..592]:malignancy:"colon cancer" (SENT (S (NP-SBJ (NP (DT:[485..488] The) (NN:[489..492] aim)) (PP (IN:[493..495] of) (NP (DT:[496..500] this) (NN:[501..506] study)))) (VP (VBD:[507..510] was) (S-NOM-PRD (NP-SBJ (-NONE-:[510..510] *)) (VP (TO:[511..513] to) (VP (VB:[514..523] elucidate) (NP (NP (DT:[524..527] the) (JJ:[528..543] transcriptional) (NNS:[545..555] mechanisms)) (PP (IN:[556..558] of) (NP (NN:[559..566] gastrin) (NN:[567..576] induction)))) (PP (IN:[577..579] in) (NP (NN:[580..585] colon) (NN:[586..592] cancer))))))) (.:[592..593] .))) ;sentence 7 Span:594..602 ;METHODS: (SENT (NP (NNS:[594..601] METHODS) (::[601..602] :))) ;sentence 8 Span:603..722 ;Gastrin messenger (mRNA) levels and K-ras genotype were determined in colon ;cancer cell lines and surgical specimens. ;[603..610]:gene-rna:"Gastrin" ;[640..645]:gene-rna:"K-ras" ;[674..686]:malignancy:"colon cancer" (SENT (S (NP-SBJ-1 (NP (NN:[603..610] Gastrin) (NN:[611..620] messenger) (PRN (-LRB-:[622..623] -LRB-) (NP (NN:[623..627] mRNA)) (-RRB-:[627..628] -RRB-)) (NNS:[629..635] levels)) (CC:[636..639] and) (NP (NN:[640..645] K-ras) (NN:[646..654] genotype))) (VP (VBD:[655..659] were) (VP (VBN:[660..670] determined) (NP-1 (-NONE-:[670..670] *)) (PP (IN:[671..673] in) (NP (NP (NML (NN:[674..679] colon) (NN:[680..686] cancer)) (NN:[687..691] cell) (NNS:[692..697] lines)) (CC:[698..701] and) (NP (JJ:[703..711] surgical) (NNS:[712..721] specimens)))))) (.:[721..722] .))) ;sentence 9 Span:723..880 ;Colon cancer cells were transfected with oncogenic ras expression vectors, ;and transcriptional activity was assayed with gastrin-luciferase reporter ;genes. ;[723..735]:malignancy:"Colon cancer" ;[774..777]:gene-rna:"ras" ;[846..853]:gene-rna:"gastrin" ;[854..864]:gene-rna:"luciferase" (SENT (S (S (NP-SBJ-2 (NN:[723..728] Colon) (NN:[729..735] cancer) (NNS:[736..741] cells)) (VP (VBD:[742..746] were) (VP (VBN:[747..758] transfected) (NP-2 (-NONE-:[758..758] *)) (PP (IN:[759..763] with) (NP (JJ:[764..773] oncogenic) (NN:[774..777] ras) (NN:[779..789] expression) (NNS:[790..797] vectors)))))) (,:[797..798] ,) (CC:[799..802] and) (S (NP-SBJ-1 (JJ:[803..818] transcriptional) (NN:[819..827] activity)) (VP (VBD:[828..831] was) (VP (VBN:[832..839] assayed) (NP-1 (-NONE-:[839..839] *)) (PP (IN:[840..844] with) (NP (NML (NN:[846..853] gastrin) (HYPH:[853..854] -) (NN:[854..864] luciferase)) (NN:[865..873] reporter) (NNS:[874..879] genes)))))) (.:[879..880] .))) ;sentence 10 Span:881..889 ;RESULTS: (SENT (NP (NNS:[881..888] RESULTS) (::[888..889] :))) ;sentence 11 Span:890..1033 ;Colon cancer cell lines and tissues with K-ras mutations all had ;significantly higher gastrin mRNA levels than those that were ras wild ;type. ;[890..902]:malignancy:"Colon cancer" ;[932..937]:gene-rna:"K-ras" ;[977..984]:gene-rna:"gastrin" ;[1019..1022]:gene-rna:"ras" (SENT (S (NP-SBJ (NP (NML (NN:[890..895] Colon) (NN:[896..902] cancer)) (NN:[903..907] cell) (NNS:[908..913] lines)) (CC:[914..917] and) (NP (NP (NNS:[918..925] tissues)) (PP (IN:[927..931] with) (NP (NN:[932..937] K-ras) (NNS:[938..947] mutations))))) (ADVP (DT:[948..951] all)) (VP (VBD:[952..955] had) (NP (NP (ADJP (RB:[956..969] significantly) (JJR:[970..976] higher)) (NN:[977..984] gastrin) (NN:[985..989] mRNA) (NNS:[990..996] levels)) (PP (IN:[997..1001] than) (NP (NP (DT:[1002..1007] those)) (SBAR (WHNP-1 (WDT:[1009..1013] that)) (S (NP-SBJ-1 (-NONE-:[1013..1013] *T*)) (VP (VBD:[1014..1018] were) (NP-PRD (NN:[1019..1022] ras) (JJ:[1023..1027] wild) (NN:[1028..1032] type))))))))) (.:[1032..1033] .))) ;sentence 12 Span:1034..1207 ;Treatment of several ras mutant cell lines with PD98059, an inhibitor of ;mitogen-activated protein kinase kinase, resulted in a decrease in ;endogenous gastrin mRNA levels. ;[1055..1058]:gene-rna:"ras" ;[1108..1147]:gene-protein:"mitogen-activated protein kinase kinase" ;[1187..1194]:gene-rna:"gastrin" (SENT (S (NP-SBJ (NP (NN:[1034..1043] Treatment)) (PP (IN:[1044..1046] of) (NP (JJ:[1047..1054] several) (NN:[1055..1058] ras) (JJ:[1059..1065] mutant) (NN:[1066..1070] cell) (NNS:[1071..1076] lines))) (PP (IN:[1077..1081] with) (NP (NP (NN:[1083..1090] PD98059)) (,:[1090..1091] ,) (NP (NP (DT:[1092..1094] an) (NN:[1095..1104] inhibitor)) (PP (IN:[1105..1107] of) (NP (ADJP (NN:[1108..1115] mitogen) (HYPH:[1115..1116] -) (VBN:[1116..1125] activated)) (NN:[1126..1133] protein) (NN:[1134..1140] kinase) (NN:[1141..1147] kinase))))))) (,:[1147..1148] ,) (VP (VBD:[1149..1157] resulted) (PP-CLR (IN:[1158..1160] in) (NP (NP (DT:[1161..1162] a) (NN:[1164..1172] decrease)) (PP (IN:[1173..1175] in) (NP (JJ:[1176..1186] endogenous) (NN:[1187..1194] gastrin) (NN:[1195..1199] mRNA) (NNS:[1200..1206] levels)))))) (.:[1206..1207] .))) ;sentence 13 Span:1208..1437 ;The effects of ras on gastrin expression appeared to be mediated through the ;gastrin promoter because transfection of oncogenic ras and activated raf ;expression vectors both induced gastrin-promoter, luciferase-reporter ;genes. ;[1223..1226]:gene-rna:"ras" ;[1230..1237]:gene-protein:"gastrin" ;[1286..1293]:gene-rna:"gastrin" ;[1338..1341]:gene-rna:"ras" ;[1356..1359]:gene-rna:"raf" ;[1393..1400]:gene-rna:"gastrin" ;[1411..1421]:gene-rna:"luciferase" (SENT (S (NP-SBJ-1 (NP (DT:[1208..1211] The) (NNS:[1212..1219] effects)) (PP (IN:[1220..1222] of) (NP (NN:[1223..1226] ras))) (PP (IN:[1227..1229] on) (NP (NN:[1230..1237] gastrin) (NN:[1239..1249] expression)))) (VP (VBD:[1250..1258] appeared) (S (NP-SBJ-1 (-NONE-:[1258..1258] *)) (VP (TO:[1259..1261] to) (VP (VB:[1262..1264] be) (VP (VBN:[1265..1273] mediated) (NP-1 (-NONE-:[1273..1273] *)) (PP (IN:[1274..1281] through) (NP (DT:[1282..1285] the) (NN:[1286..1293] gastrin) (NN:[1294..1302] promoter))))))) (SBAR-PRP (IN:[1303..1310] because) (S (NP-SBJ (NP (NN:[1312..1324] transfection)) (PP (IN:[1325..1327] of) (NP (NP (JJ:[1328..1337] oncogenic) (NN:[1338..1341] ras)) (CC:[1342..1345] and) (NP (VBN:[1346..1355] activated) (NN:[1356..1359] raf) (NN:[1360..1370] expression) (NNS:[1371..1378] vectors))))) (ADVP (DT:[1379..1383] both)) (VP (VBD:[1384..1391] induced) (NP (NML (NML (NN:[1393..1400] gastrin) (HYPH:[1400..1401] -) (NN:[1401..1409] promoter)) (,:[1409..1410] ,) (NML (NN:[1411..1421] luciferase) (HYPH:[1421..1422] -) (NN:[1422..1430] reporter))) (NNS:[1431..1436] genes)))))) (.:[1436..1437] .))) ;sentence 14 Span:1438..1585 ;The inductive effects of oncogenic ras could be blocked by the coexpression ;of dominant negative forms of raf and extracellular regulated kinase. ;[1474..1477]:gene-rna:"ras" ;[1545..1548]:gene-generic:"raf" ;[1578..1584]:gene-protein:"kinase" (SENT (S (NP-SBJ-1 (NP (DT:[1438..1441] The) (JJ:[1442..1451] inductive) (NNS:[1452..1459] effects)) (PP (IN:[1460..1462] of) (NP (JJ:[1463..1472] oncogenic) (NN:[1474..1477] ras)))) (VP (MD:[1478..1483] could) (VP (VB:[1484..1486] be) (VP (VBN:[1487..1494] blocked) (NP-1 (-NONE-:[1494..1494] *)) (PP (IN:[1495..1497] by) (NP-LGS (NP (DT:[1498..1501] the) (NN:[1502..1514] coexpression)) (PP (IN:[1515..1517] of) (NP (NP (NP (JJ:[1518..1526] dominant) (JJ:[1527..1535] negative) (NNS:[1536..1541] forms)) (PP (IN:[1542..1544] of) (NP (NN:[1545..1548] raf)))) (CC:[1549..1552] and) (NP (JJ:[1554..1567] extracellular) (VBN:[1568..1577] regulated) (NN:[1578..1584] kinase))))))))) (.:[1584..1585] .))) ;sentence 15 Span:1586..1598 ;CONCLUSIONS: (SENT (NP (NNS:[1586..1597] CONCLUSIONS) (::[1597..1598] :))) ;sentence 16 Span:1599..1712 ;Oncogenic ras induces gastrin gene expression through activation of the ;Raf-MEK-ERK signal transduction pathway. ;[1609..1612]:gene-rna:"ras" ;[1621..1628]:gene-rna:"gastrin" ;[1672..1675]:gene-rna:"Raf" ;[1676..1679]:gene-rna:"MEK" ;[1680..1683]:gene-rna:"ERK" (SENT (S (NP-SBJ (JJ:[1599..1608] Oncogenic) (NN:[1609..1612] ras)) (VP (VBZ:[1613..1620] induces) (NP (NN:[1621..1628] gastrin) (NN:[1629..1633] gene) (NN:[1635..1645] expression)) (PP (IN:[1646..1653] through) (NP (NP (NN:[1654..1664] activation)) (PP (IN:[1665..1667] of) (NP (DT:[1668..1671] the) (NML (NN:[1672..1675] Raf) (HYPH:[1675..1676] -) (NN:[1676..1679] MEK) (HYPH:[1679..1680] -) (NN:[1680..1683] ERK)) (NML (NN:[1684..1690] signal) (NN:[1691..1703] transduction)) (NN:[1704..1711] pathway)))))) (.:[1711..1712] .))) ;section 17 Span:1716..1760 ;PMID: 9797369 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1716..1720] PMID) (::[1720..1721] :) (CD:[1722..1729] 9797369) (IN:[1730..1731] -LSB-) (NNP:[1731..1737] PubMed) (HYPH:[1738..1739] -) (JJ:[1740..1747] indexed) (IN:[1748..1751] for) (NNP:[1752..1760] MEDLINE-RSB-)))