{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:37:22Z","timestamp":1781105842023,"version":"3.54.1"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,11,9]]},"abstract":"<jats:p>\n                    The enzyme poly(ADP-ribose) polymerase (Parp) catalyzes poly(ADP-ribosyl)ation reaction and is involved in DNA repair and cell death induction upon DNA damages. Meanwhile, poly(ADP-ribosyl)ation of chromosome-associated proteins is suggested to be implicated in the regulation of gene expression and cellular differentiation, both of which are important in tumorigenesis. To investigate directly the role of Parp deficiency in tumorigenicity and differentiation of embryonic stem (ES) cells during tumor formation, studies were conducted by using wild-type J1 (\n                    <jats:italic>Parp<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) ES cells and\n                    <jats:italic>Parp<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Parp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ES clones generated by disrupting\n                    <jats:italic>Parp<\/jats:italic>\n                    exon 1. These ES cells, irrespective of the Parp genotype, produced tumors phenotypically similar to teratocarcinoma when injected s.c. into nude mice. Remarkably, all tumors derived from\n                    <jats:italic>Parp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    clones contained syncytiotrophoblastic giant cells (STGCs), which possess single or multiple megalo-nuclei. The STGCs were present within large areas of intratumoral hemorrhage. In contrast, neither STGC nor hemorrhage was observed in tumors of both wild-type J1 cells and\n                    <jats:italic>Parp<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    clones. Electron microscopic examination showed that the STGCs possess microvilli on the cell surface and contained secretory granules in the cytoplasm. Furthermore, the cytoplasms of STGCs were strongly stained with antibody against mouse prolactin, which could similarly stain trophoblasts in placenta. These morphological and histochemical features indicate that the STGCs in teratocarcinoma-like tumors derived from\n                    <jats:italic>Parp<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    clones belong to the trophoblast cell lineage. Our findings thus suggest that differentiation of ES cells into STGCs was possibly induced by the lack of Parp during the development of teratocarcinoma.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.23.13345","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"13345-13350","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Syncytiotrophoblastic giant cells in teratocarcinoma-like tumors derived from\n                    <i>Parp<\/i>\n                    -disrupted mouse embryonic stem cells"],"prefix":"10.1073","volume":"96","author":[{"given":"Tadashige","family":"Nozaki","sequence":"first","affiliation":[{"name":"Division of Biochemistry, Section for Studies of Metastasis, and Common Laboratory, National Cancer Center Research Institute, 1\u20131, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045 Japan; Department of Pathology, School of Medicine, Mie University, 2\u2013174, Edobashi, Tsu, Mie 514-8507 Japan; and Chugai Pharmaceutical Co., Ltd., 1\u2013135, Komakado, Gotemba, Shizuoka, 412-0038 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuko","family":"Masutani","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Section for Studies of Metastasis, and Common Laboratory, National Cancer Center Research Institute, 1\u20131, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045 Japan; Department of Pathology, School of Medicine, Mie University, 2\u2013174, Edobashi, Tsu, Mie 514-8507 Japan; and Chugai Pharmaceutical Co., Ltd., 1\u2013135, Komakado, Gotemba, Shizuoka, 412-0038 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Section for Studies of Metastasis, and Common Laboratory, National Cancer Center Research Institute, 1\u20131, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045 Japan; Department of Pathology, School of Medicine, Mie University, 2\u2013174, Edobashi, Tsu, Mie 514-8507 Japan; and Chugai Pharmaceutical Co., Ltd., 1\u2013135, Komakado, Gotemba, Shizuoka, 412-0038 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Ochiya","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Section for Studies of Metastasis, and Common Laboratory, National Cancer Center Research Institute, 1\u20131, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045 Japan; Department of Pathology, School of Medicine, Mie University, 2\u2013174, Edobashi, Tsu, Mie 514-8507 Japan; and Chugai Pharmaceutical Co., Ltd., 1\u2013135, Komakado, Gotemba, Shizuoka, 412-0038 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumio","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Section for Studies of Metastasis, and Common Laboratory, National Cancer Center Research Institute, 1\u20131, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045 Japan; Department of Pathology, School of Medicine, Mie University, 2\u2013174, Edobashi, Tsu, Mie 514-8507 Japan; and Chugai Pharmaceutical Co., Ltd., 1\u2013135, Komakado, Gotemba, Shizuoka, 412-0038 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Nakagama","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Section for Studies of Metastasis, and Common Laboratory, National Cancer Center Research Institute, 1\u20131, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045 Japan; Department of Pathology, School of Medicine, Mie University, 2\u2013174, Edobashi, Tsu, Mie 514-8507 Japan; and Chugai Pharmaceutical Co., Ltd., 1\u2013135, Komakado, Gotemba, Shizuoka, 412-0038 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Section for 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