{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:51:11Z","timestamp":1791179471503,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,12,10]]},"abstract":"<jats:p>\n                    Retroviral elements are found in abundance throughout the human\n genome but only rarely have alterations of endogenous genes\n by retroviral insertions been described. Herein we report that a human\n endogenous retrovirus (HERV) type C is inserted in the\n human growth factor gene pleiotrophin (PTN) between the 5\u2032 untranslated\n and the coding region. This insert in the human genome expands the\n region relative to the murine gene. Studies with promoter-reporter\n constructs show that the HERV insert in the human PTN gene generates an\n additional promoter with trophoblast-specific activity. Due to this\n promoter function, fusion transcripts between HERV and the open reading\n frame of PTN (HERV-PTN) were detected in all normal human trophoblast\n cell cultures as early as 9 weeks after gestation\n (\n                    <jats:italic>n<\/jats:italic>\n                    = 7) and in all term placenta tissues\n (\n                    <jats:italic>n<\/jats:italic>\n                    = 5) but not in other normal adult tissues.\n Furthermore, only trophoblast-derived choriocarcinoma cell lines\n expressed HERV-PTN mRNA whereas tumor cell lines derived from the\n embryoblast (teratocarcinoma) or from other lineages failed to do so.\n We investigated the significance of HERV-PTN mRNA in a choriocarcinoma\n model by targeting this transcript with ribozymes and found that the\n depletion of HERV-PTN mRNA prevents human choriocarcinoma growth,\n invasion, and angiogenesis in mice. This suggests that the\n tissue-specific expression of PTN due to the HERV insertion in the\n human genome supports the highly aggressive growth of human\n choriocarcinoma and possibly of the human trophoblast.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.25.14759","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"14759-14764","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":164,"title":["Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an\u2009endogenous\u2009retrovirus"],"prefix":"10.1073","volume":"93","author":[{"given":"Anke\u2009M.","family":"Schulte","sequence":"first","affiliation":[{"name":"Lombardi Cancer Center and Department of Pharmacology, Georgetown\r University, Washington, DC 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoupeng","family":"Lai","sequence":"additional","affiliation":[{"name":"Lombardi Cancer Center and Department of Pharmacology, Georgetown\r University, Washington, DC 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Lombardi Cancer Center and Department of Pharmacology, Georgetown\r University, Washington, DC 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Czubayko","sequence":"additional","affiliation":[{"name":"Lombardi Cancer Center and Department of Pharmacology, Georgetown\r University, Washington, DC 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2009T.","family":"Riegel","sequence":"additional","affiliation":[{"name":"Lombardi Cancer Center and Department of Pharmacology, Georgetown\r University, Washington, DC 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Wellstein","sequence":"additional","affiliation":[{"name":"Lombardi Cancer Center and Department of Pharmacology, Georgetown\r University, Washington, DC 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,12,10]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2270483"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35692-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.679"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45920-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/08977199409010982"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)81267-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2661"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb08443.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00185989"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-2235(05)80005-5"},{"key":"e_1_3_2_11_2","first-page":"151","volume":"6","author":"Kurtz 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Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.25.14759","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:28:03Z","timestamp":1649860083000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.25.14759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12,10]]},"references-count":33,"journal-issue":{"issue":"25","published-print":{"date-parts":[[1996,12,10]]}},"alternative-id":["10.1073\/pnas.93.25.14759"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.25.14759","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12,10]]},"assertion":[{"value":"1996-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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