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However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp\u2013\n                    <jats:styled-content style=\"fixed-case\">TAg<\/jats:styled-content>\n                    transgenic mouse, which expresses the\n                    <jats:styled-content style=\"fixed-case\">SV40<\/jats:styled-content>\n                    large T\u2010antigen (\n                    <jats:styled-content style=\"fixed-case\">TAg<\/jats:styled-content>\n                    ) under the control of the mouse m\u00fcllerian\u2010specific\n                    <jats:italic>Ovgp\u20101<\/jats:italic>\n                    promoter. Histological analysis of the fallopian tubes of mogp\u2013\n                    <jats:styled-content style=\"fixed-case\">TAg<\/jats:styled-content>\n                    mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian\n                    <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>\n                    . We identified areas of normal\u2010appearing p53\u2010positive epithelium that are similar to \u2018p53 signatures\u2019 in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (\n                    <jats:styled-content style=\"fixed-case\">STIC<\/jats:styled-content>\n                    ), a potential precursor of ovarian\n                    <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>\n                    . Beside these non\u2010invasive precursor lesions, we also identified invasive adenocarcinoma in the ovaries of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp\u2013\n                    <jats:styled-content style=\"fixed-case\">TAg<\/jats:styled-content>\n                    and wild\u2010type (\n                    <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n                    )\n                    <jats:styled-content style=\"fixed-case\">C57BL<\/jats:styled-content>\n                    \/6. One of these genes,\n                    <jats:italic>Top2a<\/jats:italic>\n                    , which encodes topoisomerase\n                    <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , was shown by immunohistochemistry to be concurrently expressed with elevated p53 and was specifically elevated in mouse\n                    <jats:styled-content style=\"fixed-case\">STICs<\/jats:styled-content>\n                    but not in the surrounding tissues.\n                    <jats:styled-content style=\"fixed-case\">TOP2A<\/jats:styled-content>\n                    protein was also found elevated in human\n                    <jats:styled-content style=\"fixed-case\">STICs<\/jats:styled-content>\n                    , low\u2010grade and high\u2010grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive\n                    <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>\n                    in the ovary, and therefore closely simulates the current emerging model of human ovarian\n                    <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>\n                    pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumourigenesis, as well as for developing novel approaches for the prevention, diagnosis and therapy of this disease. Published 2014. This article has been contributed to by US Government employees and their work is in the public domain in the USA.\n                  <\/jats:p>","DOI":"10.1002\/path.4353","type":"journal-article","created":{"date-parts":[[2014,3,20]],"date-time":"2014-03-20T14:57:31Z","timestamp":1395327451000},"page":"228-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high\u2010grade serous carcinoma development"],"prefix":"10.1002","volume":"233","author":[{"given":"Cheryl A","family":"Sherman\u2010Baust","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology and Immunology National Institute on Aging  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Oncology and 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