{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:47:47Z","timestamp":1790480867527,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":273,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold>Endothelins (ETs) and their G protein\u2010coupled receptors exert key physiological functions during normal and aberrant placental development. Trophoblast cells mediate the contact between the embryo and the mother, by establishing a transient organ, the placenta. Choriocarcinoma cells display many of the biochemical and morphological characteristics of<jats:italic>in utero<\/jats:italic>invasive trophoblast cells and may therefore be used as a suitable model to study epithelial tumour progression of foetal\u2010derived cells.<\/jats:p><jats:p><jats:bold>Experimental approach:<\/jats:bold>The present study aimed at investigating ET receptor\u2010mediated activation of the mitogen\u2010activated protein kinase (MAPK) pathway in human choriocarcinoma.<\/jats:p><jats:p><jats:bold>Key results:<\/jats:bold>Both JAR and Jeg\u20103 choriocarcinoma cell lines expressed<jats:italic>ET receptor subtype B<\/jats:italic>(<jats:italic>ET<\/jats:italic><jats:sub><jats:italic>B<\/jats:italic><\/jats:sub>) but not<jats:italic>ET<\/jats:italic><jats:sub><jats:italic>A<\/jats:italic><\/jats:sub>receptor transcripts. ET<jats:sub>B<\/jats:sub>receptor engagement by ET\u20101 and ET\u20103 resulted in a similar time\u2010 and concentration\u2010dependent phosphorylation of p42\/44 MAPK, also known as extracellular regulated kinase 1\/2. Using specific pharmacological antagonists\/inhibitors, we showed that ET\u20101\/\u20103\u2010mediated signal transduction by the ET<jats:sub>B<\/jats:sub>receptor is transmitted via G<jats:sub>i<\/jats:sub>\u2010 and G<jats:sub>q<\/jats:sub>\u2010dependent pathways through activation of the Src (G<jats:sub>i<\/jats:sub>) and protein kinase C (G<jats:sub>q<\/jats:sub>) axis that converge at Ras\/Raf, leading to downstream activation of p42\/44. On a functional level, ET<jats:sub>B<\/jats:sub>engagement and subsequent phosphorylation of p42\/44 resulted in enhanced transcription of the immediate early response genes<jats:italic>c\u2010fos<\/jats:italic>and<jats:italic>c\u2010jun<\/jats:italic>, a process commonly assumed to be mediated by the ET<jats:sub>A<\/jats:sub>receptor, and increased cell growth and relative cell area.<\/jats:p><jats:p><jats:bold>Conclusions and implications:<\/jats:bold>As human choriocarcinoma cells secrete ETs, pharmacological antagonism of ETs and\/or ET<jats:sub>B<\/jats:sub>receptor\u2010mediated signal transduction could represent a likely target therapy for choriocarcinoma.<\/jats:p>","DOI":"10.1038\/bjp.2008.92","type":"journal-article","created":{"date-parts":[[2008,3,24]],"date-time":"2008-03-24T14:46:59Z","timestamp":1206370019000},"page":"13-24","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Endothelin (ET)\u20101 and ET\u20103 promote expression of<i>c\u2010fos<\/i>and<i>c\u2010jun<\/i>in human choriocarcinoma via ET<sub>B<\/sub>receptor\u2010mediated G<sub>i<\/sub>\u2010 and G<sub>q<\/sub>\u2010pathways and MAP kinase activation"],"prefix":"10.1111","volume":"154","author":[{"given":"A","family":"Rauh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Windischhofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Kovacevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"DeVaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Semlitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u2010J","family":"Leis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Sattler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Malle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(90)90011-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(98)00094-0"},{"key":"e_1_2_8_4_1","first-page":"6381","article-title":"Growth inhibition of cervix carcinoma cells in vivo by endothelin A receptor blockade","volume":"62","author":"Bagnato A","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.01077"},{"key":"e_1_2_8_6_1","first-page":"1306","article-title":"Activation of mitogenic signaling by endothelin 1 in ovarian carcinoma cells","volume":"57","author":"Bagnato A","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_8_7_1","volume-title":"Pathology of the Human Placenta","author":"Benirschke K","year":"2006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2016"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y06-002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0781"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.135.3.962"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2000.0542"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(02)00431-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1016-8478(23)13212-2","article-title":"c\u2010myc expression: keep the noise down","volume":"20","author":"Chung HJ","year":"2005","journal-title":"Mol Cell"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.4.671"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210421"},{"key":"e_1_2_8_17_1","first-page":"265","article-title":"Localization of fos, jun, kit and SCF mRNA in human placenta throughout gestation using in situ RT\u2010PCR","volume":"3","author":"Doneda L","year":"1997","journal-title":"Early Pregnancy"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706193"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2069"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc969"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1139\/o04-121"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199322008-00043"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1632"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(03)00097-1"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(97)00130-5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4004(94)90008-6"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/3.7.579"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi991981z"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(98)00209-6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2608"},{"key":"e_1_2_8_31_1","first-page":"E367","article-title":"Characterization and ontogeny of endothelin receptors in human placenta","volume":"264","author":"Kilpatrick SJ","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C930"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4004(97)90090-4"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.11.067"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.041951rl"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1139\/y02-006"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.32.19443"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000148703.43429.25"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7439com"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(00)00049-1"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc990"},{"key":"e_1_2_8_42_1","first-page":"663","article-title":"Endothelin\u20101 production and decreased endothelin B receptor expression in advanced prostate cancer","volume":"56","author":"Nelson JB","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1527"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90016-7"},{"key":"e_1_2_8_45_1","volume-title":"ImageJ","author":"Rasband WS","year":"1997"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.10.3331-3344.2000"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210422"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201x.1998.00368.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2006.09.026"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199800001-00041"},{"key":"e_1_2_8_51_1","first-page":"285","article-title":"Two distinct human endothelin B receptors generated by alternative splicing from a single gene","volume":"40","author":"Shyamala V","year":"1994","journal-title":"Cell Mol Biol Res"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.0102o.x"},{"key":"e_1_2_8_53_1","first-page":"5310","article-title":"Transactivation of the epidermal growth factor receptor in endothelin\u20101\u2010induced mitogenic signaling in human ovarian carcinoma cells","volume":"60","author":"Vacca F","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03394.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4004(88)90002-1"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1990.258.5.E864"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0115"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-006-9172-7"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.92","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.92","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/bjp.2008.92","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T01:22:20Z","timestamp":1708737740000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/bjp.2008.92"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,5]]}},"alternative-id":["10.1038\/bjp.2008.92"],"URL":"https:\/\/doi.org\/10.1038\/bjp.2008.92","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}