{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T08:06:40Z","timestamp":1778400400412,"version":"3.51.4"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2014,3,6]],"date-time":"2014-03-06T00:00:00Z","timestamp":1394064000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1004230","type":"journal-article","created":{"date-parts":[[2014,3,6]],"date-time":"2014-03-06T21:34:13Z","timestamp":1394141653000},"page":"e1004230","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dysregulated Estrogen Receptor Signaling in the Hypothalamic-Pituitary-Ovarian Axis Leads to Ovarian Epithelial Tumorigenesis in Mice"],"prefix":"10.1371","volume":"10","author":[{"given":"Mary J.","family":"Laws","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athilakshmi","family":"Kannan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"Pawar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanda M.","family":"Haschek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milan K.","family":"Bagchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indrani C.","family":"Bagchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,3,6]]},"reference":[{"issue":"1","key":"ref1","first-page":"10","article-title":"Cancer statistics","volume":"62","author":"R Siegel","year":"2012","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"ref2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/PGP.0b013e3181f45f3e","article-title":"The origin of ovarian carcinomas: a unifying hypothesis","volume":"30","author":"N Auersperg","year":"2011","journal-title":"Int J Gynecol Pathol"},{"key":"ref3","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":"RC Bast","year":"2009","journal-title":"Nature Reviews Cancer"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/0002-9378(75)90509-8","article-title":"Letter: the etiology and prevention of ovarian cancer","volume":"123","author":"BV Stadel","year":"1975","journal-title":"Am J Obstet Gynecol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.canlet.2012.05.017","article-title":"Gonadotropin signaling in epithelial ovarian cancer","volume":"324","author":"I Mertens-Walker","year":"2012","journal-title":"Cancer Letters"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"8177","DOI":"10.1158\/0008-5472.CAN-04-1702","article-title":"Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia","volume":"64","author":"SL Stewart","year":"2004","journal-title":"Cancer Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1046\/j.1365-2265.1998.00577.x","article-title":"Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence","volume":"49","author":"T Riman","year":"1998","journal-title":"Clin Endocrinol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1136\/bmj.2.6039.784","article-title":"Hormonal profiles after the menopause","volume":"2","author":"S Chakravarti","year":"1976","journal-title":"Br Med J"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1001\/jama.288.3.334","article-title":"Menopausal hormone replacement therapy and risk of ovarian cancer","volume":"288","author":"JV Lacey Jr","year":"2002","journal-title":"JAMA"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1001\/archinte.164.20.2253","article-title":"Hormone therapy and the impact of estrogen intake on the risk of ovarian cancer","volume":"164","author":"E Glud","year":"2004","journal-title":"Arch Intern Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/S0140-6736(07)60534-0","article-title":"Ovarian cancer and hormone replacement therapy in the Million Women Study","volume":"369","author":"V Beral","year":"2007","journal-title":"Lancet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1158\/1055-9965.EPI-07-0550","article-title":"Menopausal hormone therapy and risk of epithelial ovarian cancer","volume":"16","author":"MA Rossing","year":"2007","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1001\/jama.2009.1052","article-title":"Hormone therapy and ovarian cancer","volume":"302","author":"LS M\u00f8rch","year":"2009","journal-title":"JAMA"},{"key":"ref14","first-page":"593","article-title":"Intratumoral aromatase in human breast, endometrial, and ovarian malignancies","volume":"19","author":"H Sasano","year":"1998","journal-title":"Endocr Rev"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1290\/1071-2690(2000)036<0657:ESOOSE>2.0.CO;2","article-title":"Estrogen stimulation of ovarian surface epithelial cell proliferation","volume":"36","author":"W Bai","year":"2000","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1210\/en.2009-0602","article-title":"17beta-estradiol accelerates tumor onset and decreases survival in a transgenic mouse model of ovarian cancer","volume":"151","author":"LA Laviolette","year":"2010","journal-title":"Endocrinology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1242\/dev.127.19.4277","article-title":"Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes","volume":"127","author":"S Dupont","year":"2000","journal-title":"Development"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/gene.20098","article-title":"Cre-mediated recombination in cell lineages that express the progesterone receptor","volume":"41","author":"SM Soyal","year":"2005","journal-title":"Genesis"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0039-128X(00)00113-6","article-title":"Progesterone action and responses in the alphaERKO mouse","volume":"65","author":"SC Hewitt","year":"2000","journal-title":"Steroids"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1210\/me.2002-0398","article-title":"Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta","volume":"17","author":"JF Couse","year":"2003","journal-title":"Mol Endocrinol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1038\/sj.onc.1207721","article-title":"AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth","volume":"23","author":"DA Altomare","year":"2004","journal-title":"Oncogene"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc839","article-title":"The phosphatidylinositol 3-kinase AKT pathway in human cancer","volume":"2","author":"I Vivanco","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4505","DOI":"10.1038\/sj.onc.1207582","article-title":"Induction of hTERT expression and phosphorylation by estrogen via Akt cascade in human ovarian cancer cell lines","volume":"23","author":"A Kimura","year":"2004","journal-title":"Oncogene"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1053\/hupa.2000.18498","article-title":"Anti-Mullerian hormone is a specific marker of sertoli- and granulosa-cell origin in gonadal tumors","volume":"31","author":"R Rey","year":"2000","journal-title":"Hum Pathol"},{"key":"ref25","first-page":"255","article-title":"Ovarian surface epithelium: biology, endocrinology and pathology","volume":"22","author":"N Auersperg","year":"2001","journal-title":"Endocr Rev"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ygyno.2008.05.031","article-title":"The origin of ovarian carcinomas: a developmental view","volume":"110","author":"N Auersperg","year":"2008","journal-title":"Gynecol Oncol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.5483\/BMBRep.2011.44.7.435","article-title":"Evaluating the progenitor cells of ovarian cancer: analysis of current animal models","volume":"44","author":"SJ King","year":"2011","journal-title":"BMB reports"},{"key":"ref28","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":"RJ Kurman","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1097\/PAS.0b013e31816d71ad","article-title":"Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas","volume":"32","author":"D Nonaka","year":"2008","journal-title":"Am J Surg Pathol"},{"key":"ref30","first-page":"567","article-title":"Pax8: a marker for carcinoma of Mullerian origin in serous effusions","volume":"39","author":"GX Tong","year":"2011","journal-title":"Diagn Cytopathol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.humpath.2004.11.009","article-title":"Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRalpha, and PDGFRbeta in ovarian cancers","volume":"36","author":"SP Wilczynski","year":"2005","journal-title":"Hum Pathol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/0959-8049(94)00345-6","article-title":"Soluble intercellular adhesion molecule 1 (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumor xenogtafts","volume":"30A","author":"R Giavazzi","year":"1994","journal-title":"Eur J Cancer"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/bjc.1993.298","article-title":"Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies","volume":"68","author":"RE Banks","year":"1993","journal-title":"Br J Cancer"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1200\/JCO.2008.19.2484","article-title":"Development of a multimarker assay for early detection of ovarian cancer","volume":"28","author":"Z Yurkovetsky","year":"2010","journal-title":"J Clin Oncol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1021\/pr900411g","article-title":"Comprehensive analysis of conditioned media from ovarian cancer cell lines identifies novel candidate markers of epithelial ovarian cancer","volume":"8","author":"CG Gunawardana","year":"2009","journal-title":"J Proteome Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1158\/1078-0432.CCR-08-2403","article-title":"PPM1D (Wip1) is a potential therapeutic target in ovarian clear cell carcinomas","volume":"15","author":"DS Tan","year":"2009","journal-title":"Clin Cancer Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0039-128X(87)90029-8","article-title":"Aromatase activity in human ovarian cancer","volume":"50","author":"NJ MacLusky","year":"1987","journal-title":"Steroids"},{"key":"ref38","first-page":"6491","article-title":"Aromatization of testosterone by epithelial tumor cells cultured from patients with ovarian carcinoma","volume":"48","author":"MA Thompson","year":"1988","journal-title":"Cancer Res"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/0039-128X(89)90083-4","article-title":"Endocrine characterization of a human ovarian carcinoma (BG-1) established in nude mice","volume":"54","author":"SJ Zimniski","year":"1989","journal-title":"Steroids"},{"issue":"1","key":"ref40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ygyno.2004.03.026","article-title":"Estrogens and epithelial ovarian cancer","volume":"94","author":"S Cunata","year":"2004","journal-title":"Gynecologic Oncology"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1677\/ERC-08-0104","article-title":"Association of two common single-nucleotide polymorphisms in the CYP19A1 locus and ovarian cancer risk","volume":"15","author":"MT Goodman","year":"2008","journal-title":"Endocr Relat Cancer"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S1535-6108(01)00002-2","article-title":"Induction of ovarian cancer by defined multiple genetic changes in a mouse model system","volume":"1","author":"S Orsulic","year":"2002","journal-title":"Cancer Cell"},{"key":"ref43","first-page":"3459","article-title":"Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium","volume":"63","author":"A Flesken-Nikitin","year":"2003","journal-title":"Cancer Res"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ccr.2007.02.016","article-title":"Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt\/beta-catenin and PI3K\/Pten signaling pathways","volume":"11","author":"R Wu","year":"2007","journal-title":"Cancer Cell"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1158\/0008-5472.CAN-08-3363","article-title":"Cell type specific targeted mutation of Kras and Pten document proliferation arrest in granulosa cells versus oncogenic insult in ovarian surface epithelial cells","volume":"69","author":"HY Fan","year":"2009","journal-title":"Cancer Res"},{"key":"ref46","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":"J Kim","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/0029-7844(96)00226-8","article-title":"Epithelial ovarian cancer risk among women with polycystic ovary syndrome","volume":"88","author":"JM Schildkraut","year":"1996","journal-title":"Obstet Gynecol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1046\/j.1525-1438.1999.99075.x","article-title":"Peritoneal fluid gonadotropins and ovarian hormones in patients with ovarian cancer","volume":"9","author":"R Halperin","year":"1999","journal-title":"Int J Gynecol Cancer"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"32","DOI":"10.2298\/AOO1002032K","article-title":"Antiestrogen therapy in recurrent ovarian cancer resulting in 28 months of stable disease: a case report and review of the literature","volume":"18","author":"R Kothari","year":"2010","journal-title":"Arch Oncol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ygyno.2009.01.012","article-title":"A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer","volume":"113","author":"PA Argenta","year":"2009","journal-title":"Gynecol Oncol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/pgp.0b013e31814b191f","article-title":"Serous carcinogenesis in the fallopian tube: a descriptive classification","volume":"27","author":"E Jarboe","year":"2008","journal-title":"Int J Gynecol Pathol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma","volume":"474","year":"2011","journal-title":"Nature"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1210\/en.2011-2121","article-title":"Minireview: Animal models and mechanisms of ovarian cancer development","volume":"153","author":"LK Mullany","year":"2012","journal-title":"Endocrinology"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1053\/hupa.2001.27115","article-title":"Combined analysis of p53 and RB pathways in epithelial ovarian cancer","volume":"32","author":"Y Hashiguchi","year":"2001","journal-title":"Hum Pathol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1086\/318787","article-title":"Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer","volume":"68","author":"HA Risch","year":"2001","journal-title":"Am J Hum Genet"},{"key":"ref56","first-page":"1383","article-title":"Spontaneous ovarian tumors in Han:NMRI mice: histological classification, incidence and influence of food restriction","volume":"72","author":"S Rehm","year":"1984","journal-title":"J Natl Cancer Inst"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1289\/ehp.877391","article-title":"Ovarian neoplasms in F344 rats and B6C3F1 mice","volume":"73","author":"RH Allison","year":"1987","journal-title":"Environ Helath Perspect"},{"issue":"Suppl.2","key":"ref58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01926230490462075","article-title":"Mechanisms of hormone-mediated carcinogenesis of the ovary","volume":"32","author":"Charles C Capen","year":"2004","journal-title":"Toxicologic Pathology"},{"key":"ref59","first-page":"1283","article-title":"Hyperplastic and early neoplastic changes in the ovaries of mice after genic deletion of germ cells","volume":"48","author":"ED Murphy","year":"1972","journal-title":"J Natl Cancer Inst"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3181\/00379727-75-18222","article-title":"Ovarian and lymphoid tumors in female mice subsequent to Roentgen-ray irradiation and hormone treatment","volume":"75","author":"WU Gardner","year":"1950","journal-title":"Proc Soc Exp Biol Med"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0027-5107(95)00140-9","article-title":"Mechanisms of hormone-mediated carcinogenesis of the ovary in mice","volume":"333","author":"CC Capen","year":"1995","journal-title":"Mutation Research"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1101\/gad.1291305","article-title":"PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints","volume":"19","author":"X Lu","year":"2005","journal-title":"Genes Dev"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/ng894","article-title":"Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity","volume":"31","author":"DV Bulavin","year":"2002","journal-title":"Nat Genet"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1158\/1541-7786.MCR-08-0247","article-title":"The estrogen receptor alpha pathway induces oncogenic Wip1 phosphatase gene expression","volume":"7","author":"HS Han","year":"2009","journal-title":"Mol Cancer Res"},{"issue":"12","key":"ref65","doi-asserted-by":"crossref","first-page":"11570","DOI":"10.1074\/jbc.M311773200","article-title":"\u201cA novel pathway involving progesterone receptor, 12\/15-lipoxygenase-derived eicosanoids, and peroxisome proliferator-activated receptor gamma regulates implantation in mice.\u201d","volume":"279","author":"Q Li","year":"2004","journal-title":"J Biol Chem"}],"container-title":["PLoS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1004230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T22:52:04Z","timestamp":1648507924000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1004230"}},"subtitle":[],"editor":[{"given":"Marshall S.","family":"Horwitz","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,3,6]]},"references-count":65,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,3,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1004230","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,6]]}}}