{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:44:22Z","timestamp":1787060662104,"version":"build-2736575974"},"reference-count":34,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although named \u201covarian cancer,\u201d it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53R172H-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice.<\/jats:p>","DOI":"10.1210\/en.2014-1977","type":"journal-article","created":{"date-parts":[[2015,3,28]],"date-time":"2015-03-28T12:37:43Z","timestamp":1427546263000},"page":"1975-1981","source":"Crossref","is-referenced-by-count":75,"title":["The Ovary Is an Alternative Site of Origin for High-Grade Serous Ovarian Cancer in Mice"],"prefix":"10.1210","volume":"156","author":[{"given":"Jaeyeon","family":"Kim","sequence":"first","affiliation":[{"name":"Departments of Pathology and Immunology (J.K., L.M., M.M.M.), Weill Medical College of Cornell University, Houston, Texas 77030"},{"name":"Dan L. Duncan Cancer Center (J.K., M.M.M.), and Center for Reproductive Medicine (J.K., M.M.M.), Baylor College of Medicine; Weill Medical College of Cornell University, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Coffey","sequence":"first","affiliation":[{"name":"Departments of Pathology and Immunology (J.K., L.M., M.M.M.), Weill Medical College of Cornell University, Houston, Texas 77030"},{"name":"Department of Pathology and Genomic Medicine (D.M.C.), Houston Methodist and Weill Medical College of Cornell University, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Ma","sequence":"first","affiliation":[{"name":"Departments of Pathology and Immunology (J.K., L.M., M.M.M.), Weill Medical College of Cornell University, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M.","family":"Matzuk","sequence":"first","affiliation":[{"name":"Departments of Pathology and Immunology (J.K., L.M., M.M.M.), Weill Medical College of Cornell University, Houston, Texas 77030"},{"name":"Molecular and Cellular Biology (M.M.M.), Molecular and Human Genetics (M.M.M.), and Pharmacology (M.M.M.); Center for Drug Discovery (M.M.M.); Weill Medical College of Cornell University, Houston, Texas 77030"},{"name":"Dan L. Duncan Cancer Center (J.K., M.M.M.), and Center for Reproductive Medicine (J.K., M.M.M.), Baylor College of Medicine; Weill Medical College of Cornell University, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"key":"2020071611554888600_B1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1146\/annurev.pathol.4.110807.092246","article-title":"Ovarian cancer","volume":"4","author":"Cho","year":"2009","journal-title":"Annu Rev Pathol"},{"key":"2020071611554888600_B2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrc2644","article-title":"The biology of ovarian cancer: new opportunities for translation","volume":"9","author":"Bast","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"2020071611554888600_B3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/01.pgp.0000101080.35393.16","article-title":"The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin","volume":"23","author":"Seidman","year":"2004","journal-title":"Int J Gynecol Pathol"},{"key":"2020071611554888600_B4","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.ygyno.2010.11.020","article-title":"\u201cPrimary peritoneal\u201d high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer","volume":"120","author":"Seidman","year":"2011","journal-title":"Gynecol Oncol"},{"key":"2020071611554888600_B5","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma","volume":"474","author":"Cancer Genome Atlas Research Network","year":"2011","journal-title":"Nature"},{"key":"2020071611554888600_B6","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.2353\/ajpath.2010.100105","article-title":"Ovarian cancer development and metastasis","volume":"177","author":"Lengyel","year":"2010","journal-title":"Am J Pathol"},{"key":"2020071611554888600_B7","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1525-1438.2007.01058.x","article-title":"Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening","volume":"18","author":"Yemelyanova","year":"2008","journal-title":"Int J Gynecol Cancer"},{"key":"2020071611554888600_B8","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1200\/JCO.2004.07.179","article-title":"Biology of epithelial ovarian cancer: implications for screening women at high genetic risk","volume":"22","author":"Hogg","year":"2004","journal-title":"J Clin Oncol"},{"key":"2020071611554888600_B9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-pathol-020712-163949","article-title":"Origin and pathogenesis of pelvic (ovarian, tubal, and primary peritoneal) serous carcinoma","volume":"9","author":"Nik","year":"2014","journal-title":"Annu Rev Pathol"},{"key":"2020071611554888600_B10","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/path.1000","article-title":"Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer","volume":"195","author":"Piek","year":"2001","journal-title":"J Pathol"},{"key":"2020071611554888600_B11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3121\/cmr.2007.702","article-title":"Lessons from BRCA: the tubal fimbria emerges as an origin for pelvic serous cancer","volume":"5","author":"Crum","year":"2007","journal-title":"Clin Med Res"},{"key":"2020071611554888600_B12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/01.pas.0000213335.40358.47","article-title":"Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship","volume":"31","author":"Kindelberger","year":"2007","journal-title":"Am J Surg Pathol"},{"key":"2020071611554888600_B13","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1097\/PAS.0b013e3181ef7b16","article-title":"Are all pelvic (nonuterine) serous carcinomas of tubal origin?","volume":"34","author":"Przybycin","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"2020071611554888600_B14","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.ccr.2013.10.013","article-title":"Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models","volume":"24","author":"Perets","year":"2013","journal-title":"Cancer Cell"},{"key":"2020071611554888600_B15","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1073\/pnas.1117135109","article-title":"High-grade serous ovarian cancer arises from fallopian tube in a mouse model","volume":"109","author":"Kim","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071611554888600_B16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S1470-2045(11)70333-3","article-title":"Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project","volume":"13","author":"Gilbert","year":"2012","journal-title":"Lancet Oncol"},{"key":"2020071611554888600_B17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/path.2696","article-title":"Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary","volume":"221","author":"Ahmed","year":"2010","journal-title":"J Pathol"},{"key":"2020071611554888600_B18","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1006\/scbi.1996.0035","article-title":"The p53-deficient mouse: a model for basic and applied cancer studies","volume":"7","author":"Donehower","year":"1996","journal-title":"Semin Cancer Biol"},{"key":"2020071611554888600_B19","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2004.11.004","article-title":"Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome","volume":"119","author":"Olive","year":"2004","journal-title":"Cell"},{"key":"2020071611554888600_B20","doi-asserted-by":"crossref","first-page":"e8534","DOI":"10.1371\/journal.pone.0008534","article-title":"Conditional inactivation of Brca1, p53 and Rb in mouse ovaries results in the development of leiomyosarcomas","volume":"4","author":"Clark-Knowles","year":"2009","journal-title":"PLoS One"},{"key":"2020071611554888600_B21","doi-asserted-by":"crossref","first-page":"e8404","DOI":"10.1371\/journal.pone.0008404","article-title":"Induction of ovarian leiomyosarcomas in mice by conditional inactivation of Brca1 and p53","volume":"4","author":"Quinn","year":"2009","journal-title":"PLoS One"},{"key":"2020071611554888600_B22","doi-asserted-by":"crossref","first-page":"4621","DOI":"10.1038\/sj.onc.1204621","article-title":"Relative frequency and morphology of cancers in carriers of germline TP53 mutations","volume":"20","author":"Birch","year":"2001","journal-title":"Oncogene"},{"key":"2020071611554888600_B23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/humu.10185","article-title":"Germline TP53 mutations and Li-Fraumeni syndrome","volume":"21","author":"Varley","year":"2003","journal-title":"Hum Mutat"},{"key":"2020071611554888600_B24","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/PAS.0b013e3181cf3d79","article-title":"The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory","volume":"34","author":"Kurman","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"2020071611554888600_B25","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/mrd.20858","article-title":"A mesenchymal perspective of M\u00fcllerian duct differentiation and regression in Amhr2-lacZ mice","volume":"75","author":"Arango","year":"2008","journal-title":"Mol Reprod Dev"},{"key":"2020071611554888600_B26","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1158\/0008-5472.CAN-10-3166","article-title":"Stromal deletion of the APC tumor suppressor in mice triggers development of endometrial cancer","volume":"71","author":"Tanwar","year":"2011","journal-title":"Cancer Res"},{"key":"2020071611554888600_B27","doi-asserted-by":"crossref","first-page":"e1002906","DOI":"10.1371\/journal.pgen.1002906","article-title":"Stromal liver kinase B1 [STK11] signaling loss induces oviductal adenomas and endometrial cancer by activating mammalian target of rapamycin complex 1","volume":"8","author":"Tanwar","year":"2012","journal-title":"PLoS Genet"},{"key":"2020071611554888600_B28","doi-asserted-by":"crossref","first-page":"4951","DOI":"10.1210\/endo.136.11.7588229","article-title":"Anti-m\u00fcllerian hormone and anti-m\u00fcllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth","volume":"136","author":"Baarends","year":"1995","journal-title":"Endocrinology"},{"key":"2020071611554888600_B29","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1093\/carcin\/bgn186","article-title":"Synergistic effects of Pten loss and WNT\/CTNNB1 signaling pathway activation in ovarian granulosa cell tumor development and progression","volume":"29","author":"Lagu\u00eb","year":"2008","journal-title":"Carcinogenesis"},{"key":"2020071611554888600_B30","doi-asserted-by":"crossref","first-page":"e44285","DOI":"10.1371\/journal.pone.0044285","article-title":"Stromal-to-epithelial transition during postpartum endometrial regeneration","volume":"7","author":"Huang","year":"2012","journal-title":"PLoS One"},{"key":"2020071611554888600_B31","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1097\/AOG.0b013e3181a11c64","article-title":"Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study","volume":"113","author":"Parker","year":"2009","journal-title":"Obstet Gynecol"},{"key":"2020071611554888600_B32","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1093\/humrep\/der274","article-title":"The post-reproductive Fallopian tube: better removed?","volume":"26","author":"Dietl","year":"2011","journal-title":"Hum Reprod"},{"key":"2020071611554888600_B33","first-page":"296","article-title":"The role of the fallopian tube in ovarian cancer","volume":"10","author":"Tone","year":"2012","journal-title":"Clin Adv Hematol Oncol"},{"key":"2020071611554888600_B34","article-title":"Screening for ovarian cancer: U.S. preventive services task force reaffirmation recommendation statement","volume":"7326","author":"Moyer","year":"2012","journal-title":"Ann Intern Med"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/156\/6\/1975\/8990179\/endo1975.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/156\/6\/1975\/8990179\/endo1975.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T14:01:01Z","timestamp":1594908061000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/156\/6\/1975\/2422795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,1]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2014-1977","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,1]]}}}