{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:15:24Z","timestamp":1784207724775,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,16]]},"group-title":"In Review","reference-count":67,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,23]]},"abstract":"<title>Abstract<\/title>\n                <p>\n                  Background\n Ovarian cancer is the sixth leading cause of cancer-related deaths among women and has the highest mortality rate among gynecologic malignancies. High-grade serous ovarian carcinoma (HGSOC) is the most common and lethal subtype, accounting for approximately 70% of ovarian cancer related deaths. Increasing evidence supports the fallopian tube epithelium; not the ovarian surface epithelium; as the site of origin for HGSOC. The migration of tumorigenic fallopian tube epithelial cells to the ovary and peritoneal surfaces may be influenced by local metabolites and signaling molecules within the tumor microenvironment. While certain metabolites may promote tumorigenesis, others could exert protective effects.\nResults\n Utilizing mass spectrometry imaging (MSI), we examined the metabolic profile of co-cultures using murine ovaries and tumorigenic murine oviductal epithelial (MOE) cells harboring PTEN knockdown (MOE PTEN\n                  <sup>shRNA<\/sup>\n                  ). Among the differentially expressed metabolites, progesterone was identified to be significantly increased when tumorigenic cells were in proximity with a murine ovary. In parallel, progesterone significantly reduced the adhesion of tumorigenic cells to the murine ovary. Functionally, treatment with 100nM progesterone inhibited the migration of MOE PTEN\n                  <sup>shRNA<\/sup>\n                  cells. However, this inhibitory effect was not observed in cells harboring additional oncogenic drivers, such as mutant p53 (p53\n                  <sup>R273H<\/sup>\n                  ). RNA sequencing further revealed that progesterone treatment led to the downregulation of key angiogenesis markers in MOE PTEN\n                  <sup>shRNA<\/sup>\n                  cells. Notably, while combination treatment with progesterone and Olaparib did not alter cellular proliferation, higher concentrations of progesterone were associated with decreased expression of cancer stem cell-like markers.\nConclusion\n These findings highlight the value of utilizing fallopian tube derived tumorigenic model systems in studying HGSOC and underscore the potential role of progesterone as a modulator of tumor cell behavior. Our study provides a critical foundation for investigating hormone-mediated regulation of cell migration and its implications for ovarian cancer metastasis.\n                <\/p>","DOI":"10.21203\/rs.3.rs-9508767\/v1","type":"posted-content","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:37:49Z","timestamp":1784205469000},"source":"Crossref","is-referenced-by-count":0,"title":["Defining the Role of Progesterone Signaling in High-Grade Serous Ovarian Cancer Using Fallopian Tube Models"],"prefix":"10.21203","author":[{"given":"Diandra M. Vaval","family":"Taylor","sequence":"first","affiliation":[{"name":"University of Illinois at Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Guerrero","sequence":"additional","affiliation":[{"name":"University of California, Santa Cruz"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tova M.","family":"Bergsten","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E.","family":"Schoenhardt","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Russo","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Lantvit","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"University of California, Santa Cruz"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna E.","family":"Burdette","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"04155","DOI":"10.7189\/jogh.14.04155","article-title":"Global burden of gynaecological cancers in 2022 and projections to 2050","volume":"14","author":"Zhu B","year":"2024","unstructured":"Zhu B, Gu H, Mao Z, et al. Global burden of gynaecological cancers in 2022 and projections to 2050. J Glob Health. 2024;14:04155. 10.7189\/jogh.14.04155.","journal-title":"J Glob Health"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31551","author":"Cronin KA","year":"2018","unstructured":"Cronin KA, Lake AJ, Scott S et al. Annual report to the nation on the status of cancer, part I: National cancer statistics. Cancer. 2018;124(13):2785\u20132800. 10.1002\/cncr.31551"},{"issue":"1","key":"ref3","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1038\/s41467-017-00962-1","article-title":"High grade serous ovarian carcinomas originate in the fallopian tube","volume":"8","author":"Labidi-Galy SI","year":"2017","unstructured":"Labidi-Galy SI, Papp E, Hallberg D, et al. High grade serous ovarian carcinomas originate in the fallopian tube. Nat Commun. 2017;8(1):1093\u20131. 10.1038\/s41467-017-00962-1.","journal-title":"Nat Commun"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1556377","DOI":"10.3389\/fimmu.2025.1556377","article-title":"Unveiling drug resistance pathways in high-grade serous ovarian cancer(HGSOC): Recent advances and future perspectives","volume":"16","author":"Fu R","year":"2025","unstructured":"Fu R, Hu R, Li W, Lv X, Zhao H, Li F. Unveiling drug resistance pathways in high-grade serous ovarian cancer(HGSOC): Recent advances and future perspectives. Front Immunol. 2025;16:1556377. 10.3389\/fimmu.2025.1556377.","journal-title":"Front Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.canlet.2020.02.017","article-title":"Fallopian tube initiation of high grade serous ovarian cancer and ovarian metastasis: Mechanisms and therapeutic implications","volume":"476","author":"Bergsten TM","year":"2020","unstructured":"Bergsten TM, Burdette JE, Dean M. Fallopian tube initiation of high grade serous ovarian cancer and ovarian metastasis: Mechanisms and therapeutic implications. Cancer Lett. 2020;476:152\u201360. 10.1016\/j.canlet.2020.02.017.","journal-title":"Cancer Lett"},{"issue":"7","key":"ref6","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1002\/ijc.29528","article-title":"Mutant p53 expression in fallopian tube epithelium drives cell migration","volume":"137","author":"Quartuccio SM","year":"2015","unstructured":"Quartuccio SM, Karthikeyan S, Eddie SL, et al. Mutant p53 expression in fallopian tube epithelium drives cell migration. Int J Cancer. 2015;137(7):1528\u201338. 10.1002\/ijc.29528.","journal-title":"Int J Cancer"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3389\/fonc.2015.00154","article-title":"Spontaneous transformation of murine oviductal epithelial cells: A model system to investigate the onset of fallopian-derived tumors","volume":"5","author":"Endsley MP","year":"2015","unstructured":"Endsley MP, Moyle-Heyrman G, Karthikeyan S, et al. Spontaneous transformation of murine oviductal epithelial cells: A model system to investigate the onset of fallopian-derived tumors. Front Oncol. 2015;5:154. 10.3389\/fonc.2015.00154.","journal-title":"Front Oncol"},{"issue":"10","key":"ref8","doi-asserted-by":"publisher","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 J","year":"2012","unstructured":"Kim J, Coffey DM, Creighton CJ, Yu Z, Hawkins SM, Matzuk MM. High-grade serous ovarian cancer arises from fallopian tube in a mouse model. Proc Natl Acad Sci U S A. 2012;109(10):3921\u20136. 10.1073\/pnas.1117135109.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"24","key":"ref9","doi-asserted-by":"publisher","first-page":"20500","DOI":"10.18632\/oncotarget.3985","article-title":"Tumorigenesis and peritoneal colonization from fallopian tube epithelium","volume":"6","author":"Eddie SL","year":"2015","unstructured":"Eddie SL, Quartuccio SM, \u00d3 hAinmhir E, et al. Tumorigenesis and peritoneal colonization from fallopian tube epithelium. Oncotarget. 2015;6(24):20500\u201312. 10.18632\/oncotarget.3985.","journal-title":"Oncotarget"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1328651","DOI":"10.3389\/fimmu.2023.1328651","article-title":"Targeting the immune microenvironment for ovarian cancer therapy","volume":"14","author":"Blanc-Durand F","year":"2023","unstructured":"Blanc-Durand F, Clemence Wei Xian L, Tan DSP. Targeting the immune microenvironment for ovarian cancer therapy. Front Immunol. 2023;14:1328651. 10.3389\/fimmu.2023.1328651.","journal-title":"Front Immunol"},{"issue":"6","key":"ref11","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1158\/2767-9764.crc-22-0017","article-title":"The tumor immune profile of murine ovarian cancer models: An essential tool for ovarian cancer immunotherapy research","volume":"2","author":"Rodriguez GM","year":"2022","unstructured":"Rodriguez GM, Galpin KJC, Cook DP, et al. The tumor immune profile of murine ovarian cancer models: An essential tool for ovarian cancer immunotherapy research. Cancer Res Commun. 2022;2(6):417\u201333. 10.1158\/2767-9764.crc-22-0017.","journal-title":"Cancer Res Commun"},{"issue":"8932","key":"ref12","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1016\/s0140-6736(94)90749-8","article-title":"Parity, age at first childbirth, and risk of ovarian cancer","volume":"344","author":"Adami HO","year":"1994","unstructured":"Adami HO, Hsieh CC, Lambe M, et al. Parity, age at first childbirth, and risk of ovarian cancer. Lancet. 1994;344(8932):1250\u20134. 10.1016\/s0140-6736(94)90749-8.","journal-title":"Lancet"},{"issue":"9574","key":"ref13","doi-asserted-by":"publisher","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":"Beral V","year":"2007","unstructured":"Beral V, Million Women Study Collaborators, Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the million women study. Lancet. 2007;369(9574):1703\u201310. 10.1016\/S0140-6736(07)60534-0.","journal-title":"Lancet"},{"issue":"1","key":"ref14","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1093\/jnci\/94.1.32","article-title":"Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk","volume":"94","author":"Schildkraut JM","year":"2002","unstructured":"Schildkraut JM, Calingaert B, Marchbanks PA, Moorman PG, Rodriguez GC. Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk. J Natl Cancer Inst. 2002;94(1):32\u20138. 10.1093\/jnci\/94.1.32.","journal-title":"J Natl Cancer Inst"},{"issue":"1\u20133","key":"ref15","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0960-0760(91)90192-8","article-title":"Progestin receptors: Isoforms and antihormone action","volume":"40","author":"Gronemeyer H","year":"1991","unstructured":"Gronemeyer H, Meyer ME, Bocquel MT, Kastner P, Turcotte B, Chambon P. Progestin receptors: Isoforms and antihormone action. J Steroid Biochem Mol Biol. 1991;40(1\u20133):271\u20138. 10.1016\/0960-0760(91)90192-8.","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"7","key":"ref16","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1210\/clinem\/dgab195","article-title":"Progesterone receptors promote quiescence and ovarian cancer cell phenotypes via DREAM in p53-mutant fallopian tube models","volume":"106","author":"Mauro LJ","year":"2021","unstructured":"Mauro LJ, Seibel MI, Diep CH, et al. Progesterone receptors promote quiescence and ovarian cancer cell phenotypes via DREAM in p53-mutant fallopian tube models. J Clin Endocrinol Metab. 2021;106(7):1929\u201355. 10.1210\/clinem\/dgab195.","journal-title":"J Clin Endocrinol Metab"},{"issue":"21","key":"ref17","doi-asserted-by":"publisher","first-page":"3456","DOI":"10.3390\/cancers17213456","article-title":"Medroxyprogesterone acetate inhibits tumorigenesis in mouse models of oviductal high-grade serous carcinoma","volume":"17","author":"Zhai Y","year":"2025","unstructured":"Zhai Y, Bedi K, Wu R, et al. Medroxyprogesterone acetate inhibits tumorigenesis in mouse models of oviductal high-grade serous carcinoma. Cancers (Basel). 2025;17(21):3456. 10.3390\/cancers17213456.","journal-title":"Cancers (Basel)"},{"issue":"14","key":"ref18","doi-asserted-by":"publisher","first-page":"11823","DOI":"10.3390\/ijms241411823","article-title":"Effects of the overexpression of progesterone receptors on a precancer p53 and rb-defective human fallopian tube epithelial cell line","volume":"24","author":"Chang Y","year":"2023","unstructured":"Chang Y, Wu K, Wang K, Ding D. Effects of the overexpression of progesterone receptors on a precancer p53 and rb-defective human fallopian tube epithelial cell line. Int J Mol Sci. 2023;24(14):11823. 10.3390\/ijms241411823.","journal-title":"Int J Mol Sci"},{"issue":"4","key":"ref19","doi-asserted-by":"publisher","first-page":"106523","DOI":"10.1016\/j.isci.2023.106523","article-title":"Progesterone prevents HGSOC by promoting precancerous cell pyroptosis via inducing fibroblast paracrine","volume":"26","author":"Wu N","year":"2023","unstructured":"Wu N, Zhang X, Wang Z, et al. Progesterone prevents HGSOC by promoting precancerous cell pyroptosis via inducing fibroblast paracrine. iScience. 2023;26(4):106523. 10.1016\/j.isci.2023.106523.","journal-title":"iScience"},{"issue":"1","key":"ref20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/carcin\/bgy170","article-title":"Exposure of the extracellular matrix and colonization of the ovary in metastasis of fallopian-tube-derived cancer","volume":"40","author":"Dean M","year":"2019","unstructured":"Dean M, Jin V, Russo A, Lantvit DD, Burdette JE. Exposure of the extracellular matrix and colonization of the ovary in metastasis of fallopian-tube-derived cancer. Carcinogenesis. 2019;40(1):41\u201351. 10.1093\/carcin\/bgy170.","journal-title":"Carcinogenesis"},{"issue":"1","key":"ref21","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/107155760301000110","article-title":"Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines","volume":"10","author":"Smid-Koopman E","year":"2003","unstructured":"Smid-Koopman E, Blok LJ, K\u00fchne LCM, et al. Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. J Soc Gynecol Investig. 2003;10(1):49\u201357.","journal-title":"J Soc Gynecol Investig"},{"issue":"10","key":"ref22","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1021\/acscentsci.8b00405","article-title":"Imaging mass spectrometry reveals crosstalk between the fallopian tube and the ovary that drives primary metastasis of ovarian cancer","volume":"4","author":"Zink KE","year":"2018","unstructured":"Zink KE, Dean M, Burdette JE, Sanchez LM. Imaging mass spectrometry reveals crosstalk between the fallopian tube and the ovary that drives primary metastasis of ovarian cancer. ACS Cent Sci. 2018;4(10):1360\u201370. 10.1021\/acscentsci.8b00405.","journal-title":"ACS Cent Sci"},{"issue":"13","key":"ref23","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","article-title":"New colorimetric cytotoxicity assay for anticancer-drug screening","volume":"82","author":"Skehan P","year":"1990","unstructured":"Skehan P, Storeng R, Scudiero D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990;82(13):1107\u201312. 10.1093\/jnci\/82.13.1107.","journal-title":"J Natl Cancer Inst"},{"issue":"1","key":"ref24","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1021\/acs.jnatprod.1c01008","article-title":"The flavonoid baicalein negatively regulates progesterone target genes in the uterus in vivo","volume":"85","author":"Li K","year":"2022","unstructured":"Li K, Diakite D, Austin J, et al. The flavonoid baicalein negatively regulates progesterone target genes in the uterus in vivo. J Nat Prod. 2022;85(1):237\u201347. 10.1021\/acs.jnatprod.1c01008.","journal-title":"J Nat Prod"},{"issue":"2","key":"ref25","doi-asserted-by":"publisher","first-page":"dju410","DOI":"10.1093\/jnci\/dju410","article-title":"Ovarian cancer risk after salpingectomy: A nationwide population-based study","volume":"107","author":"Falconer H","year":"2015","unstructured":"Falconer H, Yin L, Gr\u00f6nberg H, Altman D. Ovarian cancer risk after salpingectomy: A nationwide population-based study. J Natl Cancer Inst. 2015;107(2):dju410. 10.1093\/jnci\/dju410. Print 2015 Feb.","journal-title":"J Natl Cancer Inst"},{"issue":"9","key":"ref26","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1158\/1541-7786.MCR-16-0097","article-title":"DNA methylome analyses implicate fallopian tube epithelia as the origin for high-grade serous ovarian cancer","volume":"14","author":"Klinkebiel D","year":"2016","unstructured":"Klinkebiel D, Zhang W, Akers SN, Odunsi K, Karpf AR. DNA methylome analyses implicate fallopian tube epithelia as the origin for high-grade serous ovarian cancer. Mol Cancer Res. 2016;14(9):787\u201394. 10.1158\/1541-7786.MCR-16-0097.","journal-title":"Mol Cancer Res"},{"issue":"17","key":"ref27","doi-asserted-by":"publisher","first-page":"6116","DOI":"10.1158\/1078-0432.CCR-04-2509","article-title":"Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon","volume":"11","author":"Marquez RT","year":"2005","unstructured":"Marquez RT, Baggerly KA, Patterson AP, et al. Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon. Clin Cancer Res. 2005;11(17):6116\u201326. 10.1158\/1078-0432.CCR-04-2509.","journal-title":"Clin Cancer Res"},{"issue":"1","key":"ref28","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ajpath.2020.09.006","article-title":"The origin of ovarian cancer species and precancerous landscape","volume":"191","author":"Shih I","year":"2021","unstructured":"Shih I, Wang Y, Wang T. The origin of ovarian cancer species and precancerous landscape. Am J Pathol. 2021;191(1):26\u201339. 10.1016\/j.ajpath.2020.09.006.","journal-title":"Am J Pathol"},{"issue":"5","key":"ref29","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.ajog.2013.04.019","article-title":"The role of the fallopian tube in the origin of ovarian cancer","volume":"209","author":"Erickson BK","year":"2013","unstructured":"Erickson BK, Conner MG, Landen CNJ. The role of the fallopian tube in the origin of ovarian cancer. Am J Obstet Gynecol. 2013;209(5):409\u201314. 10.1016\/j.ajog.2013.04.019.","journal-title":"Am J Obstet Gynecol"},{"issue":"146","key":"ref30","doi-asserted-by":"publisher","DOI":"10.3791\/59490","article-title":"Capturing small molecule communication between tissues and cells using imaging mass spectrometry","author":"Zink KE","year":"2019","unstructured":"Zink KE, Dean M, Burdette JE, Sanchez LM. Capturing small molecule communication between tissues and cells using imaging mass spectrometry. J Vis Exp. 2019;14610.3791\/59490.","journal-title":"J Vis Exp"},{"issue":"7","key":"ref31","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1021\/acsptsci.4c00238","article-title":"Fallopian tube-derived high-grade serous cancers influence ovarian production of norepinephrine and generate specific metabolomic signatures","volume":"7","author":"Bergsten TM","year":"2024","unstructured":"Bergsten TM, Lusk HJ, Haughan MA, et al. Fallopian tube-derived high-grade serous cancers influence ovarian production of norepinephrine and generate specific metabolomic signatures. ACS Pharmacol Transl Sci. 2024;7(7):2185\u201395. 10.1021\/acsptsci.4c00238.","journal-title":"ACS Pharmacol Transl Sci"},{"issue":"15","key":"ref32","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1038\/s41388-017-0097-8","article-title":"PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation","volume":"37","author":"Russo A","year":"2018","unstructured":"Russo A, Czarnecki AA, Dean M, et al. PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation. Oncogene. 2018;37(15):1976\u201390. 10.1038\/s41388-017-0097-8.","journal-title":"Oncogene"},{"key":"ref33","first-page":"291","article-title":"The A and B isoforms of the human progesterone receptor: Two functionally different transcription factors encoded by a single gene","volume":"54","author":"Giangrande PH","year":"1999","unstructured":"Giangrande PH, McDonnell DP. The A and B isoforms of the human progesterone receptor: Two functionally different transcription factors encoded by a single gene. Recent Prog Horm Res. 1999;54:291\u20134.","journal-title":"Recent Prog Horm Res"},{"issue":"6","key":"ref34","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1186\/bcr539","article-title":"Progesterone receptors\u2013animal models and cell signalling in breast cancer. diverse activation pathways for the progesterone receptor: Possible implications for breast biology and cancer","volume":"4","author":"Lanari C","year":"2002","unstructured":"Lanari C, Molinolo AA. Progesterone receptors\u2013animal models and cell signalling in breast cancer. diverse activation pathways for the progesterone receptor: Possible implications for breast biology and cancer. Breast Cancer Res. 2002;4(6):240\u20133. 10.1186\/bcr539.","journal-title":"Breast Cancer Res"},{"issue":"10\u201311","key":"ref35","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/s0039-128x(00)00112-4","article-title":"Progesterone receptor coactivators","volume":"65","author":"Rowan BG","year":"2000","unstructured":"Rowan BG, O'Malley BW. Progesterone receptor coactivators. Steroids. 2000;65(10\u201311):545\u20139. 10.1016\/s0039-128x(00)00112-4.","journal-title":"Steroids"},{"issue":"4","key":"ref36","first-page":"435","article-title":"Transcriptional activation of nuclear estrogen receptor and progesterone receptor and its regulation","volume":"68","author":"Xin Q","year":"2016","unstructured":"Xin Q, Qiu J, Cui S, Xia G, Wang H. Transcriptional activation of nuclear estrogen receptor and progesterone receptor and its regulation. Sheng Li Xue Bao. 2016;68(4):435\u201354.","journal-title":"Sheng Li Xue Bao"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"0371","DOI":"10.34133\/research.0371","article-title":"Progesterone enhances niraparib efficacy in ovarian cancer by promoting palmitoleic-acid-mediated ferroptosis","volume":"7","author":"Wu N","year":"2024","unstructured":"Wu N, Zhang X, Fang C, et al. Progesterone enhances niraparib efficacy in ovarian cancer by promoting palmitoleic-acid-mediated ferroptosis. Res (Wash D C). 2024;7:0371. 10.34133\/research.0371.","journal-title":"Res (Wash D C)"},{"issue":"6","key":"ref38","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1210\/endo-101-6-1850","article-title":"Properties of the cytoplasmic progestin-binding protein in the rabbit uterus","volume":"101","author":"Philibert D","year":"1977","unstructured":"Philibert D, Ojasoo T, Raynaud J. Properties of the cytoplasmic progestin-binding protein in the rabbit uterus. Endocrinology. 1977;101(6):1850\u201361. 10.1210\/endo-101-6-1850.","journal-title":"Endocrinology"},{"issue":"1","key":"ref39","doi-asserted-by":"publisher","first-page":"e13071","DOI":"10.1111\/jne.13071","article-title":"Progesterone receptor-src kinase signaling pathway mediates neuroprogesterone induction of the luteinizing hormone surge in female rats","volume":"34","author":"Chuon T","year":"2022","unstructured":"Chuon T, Feri M, Carlson C, Ondrejik S, Micevych PE, Sinchak K. Progesterone receptor-src kinase signaling pathway mediates neuroprogesterone induction of the luteinizing hormone surge in female rats. J Neuroendocrinol. 2022;34(1):e13071. 10.1111\/jne.13071.","journal-title":"J Neuroendocrinol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.steroids.2016.09.004","article-title":"Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER\/PR target genes","volume":"114","author":"Diep CH","year":"2016","unstructured":"Diep CH, Ahrendt H, Lange CA. Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER\/PR target genes. Steroids. 2016;114:48\u201358. 10.1016\/j.steroids.2016.09.004.","journal-title":"Steroids"},{"issue":"8","key":"ref41","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3390\/cancers10080262","article-title":"UnPAXing the divergent roles of PAX2 and PAX8 in high-grade serous ovarian cancer","volume":"10","author":"Hardy LR","year":"2018","unstructured":"Hardy LR, Salvi A, Burdette JE. UnPAXing the divergent roles of PAX2 and PAX8 in high-grade serous ovarian cancer. Cancers (Basel). 2018;10(8):262. 10.3390\/cancers10080262.","journal-title":"Cancers (Basel)"},{"issue":"6","key":"ref42","doi-asserted-by":"publisher","first-page":"189224","DOI":"10.1016\/j.bbcan.2024.189224","article-title":"Biomarkers in high grade serous ovarian cancer","volume":"1879","author":"Bates M","year":"2024","unstructured":"Bates M, Mohamed BM, Lewis F, O'Toole S, O'Leary JJ. Biomarkers in high grade serous ovarian cancer. Biochim Biophys Acta Rev Cancer. 2024;1879(6):189224. 10.1016\/j.bbcan.2024.189224.","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"100866","DOI":"10.1016\/j.neo.2022.100866","article-title":"PAX8 modulates the tumor microenvironment of high grade serous ovarian cancer through changes in the secretome","volume":"36","author":"Salvi A","year":"2023","unstructured":"Salvi A, Hardy LR, Heath KN, et al. PAX8 modulates the tumor microenvironment of high grade serous ovarian cancer through changes in the secretome. Neoplasia. 2023;36:100866. 10.1016\/j.neo.2022.100866.","journal-title":"Neoplasia"},{"issue":"6","key":"ref44","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1210\/mend.9.6.8592515","article-title":"Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus","volume":"9","author":"Das SK","year":"1995","unstructured":"Das SK, Chakraborty I, Paria BC, Wang XN, Plowman G, Dey SK. Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus. Mol Endocrinol. 1995;9(6):691\u2013705. 10.1210\/mend.9.6.8592515.","journal-title":"Mol Endocrinol"},{"issue":"7","key":"ref45","doi-asserted-by":"publisher","first-page":"3646","DOI":"10.1073\/pnas.96.7.3646","article-title":"Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor alpha knockout mouse uterus","volume":"96","author":"Curtis SW","year":"1999","unstructured":"Curtis SW, Clark J, Myers P, Korach KS. Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor alpha knockout mouse uterus. Proc Natl Acad Sci U S A. 1999;96(7):3646\u201351. 10.1073\/pnas.96.7.3646.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"111826","DOI":"10.1016\/j.mce.2022.111826","article-title":"AREG upregulates secreted protein acidic and rich in cysteine expression in human granulosa cells","volume":"561","author":"Dang X","year":"2023","unstructured":"Dang X, Fang L, Zhang Q, Liu B, Cheng J, Sun Y. AREG upregulates secreted protein acidic and rich in cysteine expression in human granulosa cells. Mol Cell Endocrinol. 2023;561:111826. 10.1016\/j.mce.2022.111826.","journal-title":"Mol Cell Endocrinol"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2014.09.009","author":"Moore NL","year":"2014","unstructured":"Moore NL, Edwards DP, Weigel NL. Cyclin A2 and its associated kinase activity are required for optimal induction of progesterone receptor target genes in breast cancer cells. J Steroid Biochem Mol Biol. 2014;144 Pt B(0 0):471\u2013482. 10.1016\/j.jsbmb.2014.09.009"},{"issue":"4","key":"ref48","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.coph.2011.04.006","article-title":"Steroid up-regulation of FKBP51 and its role in hormone signaling","volume":"11","author":"J\u00e4\u00e4skel\u00e4inen T","year":"2011","unstructured":"J\u00e4\u00e4skel\u00e4inen T, Makkonen H, Palvimo JJ. Steroid up-regulation of FKBP51 and its role in hormone signaling. Curr Opin Pharmacol. 2011;11(4):326\u201331. 10.1016\/j.coph.2011.04.006.","journal-title":"Curr Opin Pharmacol"},{"issue":"12","key":"ref49","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.4161\/cbt.6.12.4976","article-title":"PDGF BB induces VEGF secretion in ovarian cancer","volume":"6","author":"Matei D","year":"2007","unstructured":"Matei D, Kelich S, Cao L, et al. PDGF BB induces VEGF secretion in ovarian cancer. Cancer Biol Ther. 2007;6(12):1951\u20139. 10.4161\/cbt.6.12.4976.","journal-title":"Cancer Biol Ther"},{"issue":"8","key":"ref50","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.3390\/cancers12082063","article-title":"Carcinoma-associated mesenchymal stem cells promote chemoresistance in ovarian cancer stem cells via PDGF signaling","volume":"12","author":"Raghavan S","year":"2020","unstructured":"Raghavan S, Snyder CS, Wang A, et al. Carcinoma-associated mesenchymal stem cells promote chemoresistance in ovarian cancer stem cells via PDGF signaling. Cancers (Basel). 2020;12(8):2063. 10.3390\/cancers12082063.","journal-title":"Cancers (Basel)"},{"issue":"1","key":"ref51","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10549-022-06661-w","article-title":"Intratumoral PDGFB gene predominantly expressed in endothelial cells is associated with angiogenesis and lymphangiogenesis, but not with metastasis in breast cancer","volume":"195","author":"Wu R","year":"2022","unstructured":"Wu R, Gandhi S, Tokumaru Y, et al. Intratumoral PDGFB gene predominantly expressed in endothelial cells is associated with angiogenesis and lymphangiogenesis, but not with metastasis in breast cancer. Breast Cancer Res Treat. 2022;195(1):17\u201331. 10.1007\/s10549-022-06661-w.","journal-title":"Breast Cancer Res Treat"},{"issue":"1","key":"ref52","doi-asserted-by":"publisher","first-page":"e101806","DOI":"10.7759\/cureus.101806","article-title":"Progesterone enhances the sensitivity of ovarian cancer cells to poly (ADP-ribose) polymerase (PARP) inhibitors by suggesting a role for transcription-replication conflict-related pathways: An in vitro study","volume":"18","author":"Suizu E","year":"2026","unstructured":"Suizu E, Koyanagi T, Saga Y, et al. Progesterone enhances the sensitivity of ovarian cancer cells to poly (ADP-ribose) polymerase (PARP) inhibitors by suggesting a role for transcription-replication conflict-related pathways: An in vitro study. Cureus. 2026;18(1):e101806. 10.7759\/cureus.101806.","journal-title":"Cureus"},{"issue":"4","key":"ref53","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41419-021-03663-2","article-title":"Silencing PTEN in the fallopian tube promotes enrichment of cancer stem cell-like function through loss of PAX2","volume":"12","author":"Russo A","year":"2021","unstructured":"Russo A, Colina JA, Moy J, et al. Silencing PTEN in the fallopian tube promotes enrichment of cancer stem cell-like function through loss of PAX2. Cell Death Dis. 2021;12(4):375\u20132. 10.1038\/s41419-021-03663-2.","journal-title":"Cell Death Dis"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"108680","DOI":"10.1016\/j.steroids.2020.108680","article-title":"Progesterone decreases ovarian cancer cells migration and invasion","volume":"161","author":"Lima MA","year":"2020","unstructured":"Lima MA, Silva SV, Jaeger RG, Freitas VM. Progesterone decreases ovarian cancer cells migration and invasion. Steroids. 2020;161:108680. 10.1016\/j.steroids.2020.108680.","journal-title":"Steroids"},{"issue":"6","key":"ref55","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1210\/endrev\/bnad018","article-title":"Reevaluating the role of progesterone in ovarian cancer: Is progesterone always protective?","volume":"44","author":"Mauro LJ","year":"2023","unstructured":"Mauro LJ, Spartz A, Austin JR, Lange CA. Reevaluating the role of progesterone in ovarian cancer: Is progesterone always protective? Endocr Rev. 2023;44(6):1029\u201346. 10.1210\/endrev\/bnad018.","journal-title":"Endocr Rev"},{"issue":"2","key":"ref56","doi-asserted-by":"publisher","first-page":"113","DOI":"10.15430\/jcp.2013.18.2.113","article-title":"Protective effect of progesterone during pregnancy against ovarian cancer","volume":"18","author":"Han KH","year":"2013","unstructured":"Han KH, Kim M, Kim HS, Chung HH, Song YS. Protective effect of progesterone during pregnancy against ovarian cancer. J Cancer Prev. 2013;18(2):113\u201322. 10.15430\/jcp.2013.18.2.113.","journal-title":"J Cancer Prev"},{"issue":"11","key":"ref57","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1016\/j.celrep.2017.02.049","article-title":"Progesterone prevents high-grade serous ovarian cancer by inducing necroptosis of p53-defective fallopian tube epithelial cells","volume":"18","author":"Wu N","year":"2017","unstructured":"Wu N, Huang H, Chao TH, et al. Progesterone prevents high-grade serous ovarian cancer by inducing necroptosis of p53-defective fallopian tube epithelial cells. Cell Rep. 2017;18(11):2557\u201365. 10.1016\/j.celrep.2017.02.049.","journal-title":"Cell Rep"},{"issue":"21","key":"ref58","doi-asserted-by":"publisher","first-page":"5578","DOI":"10.3390\/cancers13215578","article-title":"Highly expressed progesterone receptor B isoform increases platinum sensitivity and survival of ovarian high-grade serous carcinoma","volume":"13","author":"Lin H","year":"2021","unstructured":"Lin H, Lan K, Ou Y, et al. Highly expressed progesterone receptor B isoform increases platinum sensitivity and survival of ovarian high-grade serous carcinoma. Cancers (Basel). 2021;13(21):5578. 10.3390\/cancers13215578.","journal-title":"Cancers (Basel)"},{"issue":"50","key":"ref59","doi-asserted-by":"publisher","first-page":"31993","DOI":"10.1073\/pnas.2013595117","article-title":"Targeting progesterone signaling prevents metastatic ovarian cancer","volume":"117","author":"Kim O","year":"2020","unstructured":"Kim O, Park EY, Kwon SY, et al. Targeting progesterone signaling prevents metastatic ovarian cancer. Proc Natl Acad Sci U S A. 2020;117(50):31993\u20132004. 10.1073\/pnas.2013595117.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ref60","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s41379-019-0370-1","article-title":"Natural history of ovarian high-grade serous carcinoma from time effects of ovulation inhibition and progesterone clearance of p53-defective lesions","volume":"33","author":"Wu NY","year":"2020","unstructured":"Wu NY, Fang C, Huang H, Wang J, Chu T. Natural history of ovarian high-grade serous carcinoma from time effects of ovulation inhibition and progesterone clearance of p53-defective lesions. Mod Pathol. 2020;33(1):29\u201337. 10.1038\/s41379-019-0370-1.","journal-title":"Mod Pathol"},{"issue":"40","key":"ref61","doi-asserted-by":"publisher","first-page":"64836","DOI":"10.18632\/oncotarget.11711","article-title":"Ovarian hormones through wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions","volume":"7","author":"Nagendra PB","year":"2016","unstructured":"Nagendra PB, Goad J, Nielsen S, et al. Ovarian hormones through wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions. Oncotarget. 2016;7(40):64836\u201353. 10.18632\/oncotarget.11711.","journal-title":"Oncotarget"},{"issue":"8","key":"ref62","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.3390\/cancers14081947","article-title":"Platelet-derived PDGFB promotes recruitment of cancer-associated fibroblasts, deposition of extracellular matrix and tgf\u03b2 signaling in the tumor microenvironment","volume":"14","author":"Zhang Y","year":"2022","unstructured":"Zhang Y, Manouchehri Doulabi E, Herre M, et al. Platelet-derived PDGFB promotes recruitment of cancer-associated fibroblasts, deposition of extracellular matrix and tgf\u03b2 signaling in the tumor microenvironment. Cancers (Basel). 2022;14(8):1947. 10.3390\/cancers14081947.","journal-title":"Cancers (Basel)"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ygyno.2026.02.033","article-title":"Progestin and vitamin D synergistically inhibit fallopian tube carcinogenesis","volume":"208","author":"Nelson OL","year":"2026","unstructured":"Nelson OL, Rosales R, Turbov J, et al. Progestin and vitamin D synergistically inhibit fallopian tube carcinogenesis. Gynecol Oncol. 2026;208:8\u201316. 10.1016\/j.ygyno.2026.02.033.","journal-title":"Gynecol Oncol"},{"issue":"4","key":"ref64","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1158\/2767-9764.CRC-24-0532","article-title":"Branched-chain amino acid catabolism promotes ovarian cancer cell proliferation via phosphorylation of mTOR","volume":"5","author":"Lusk HJ","year":"2025","unstructured":"Lusk HJ, Haughan MA, Bergsten TM, Burdette JE, Sanchez LM. Branched-chain amino acid catabolism promotes ovarian cancer cell proliferation via phosphorylation of mTOR. Cancer Res Commun. 2025;5(4):569\u201379. 10.1158\/2767-9764.CRC-24-0532.","journal-title":"Cancer Res Commun"},{"issue":"5","key":"ref65","doi-asserted-by":"publisher","first-page":"e170961","DOI":"10.1172\/jci.insight.170961","article-title":"Norepinephrine induces anoikis resistance in high-grade serous ovarian cancer precursor cells","volume":"9","author":"Reavis HD","year":"2024","unstructured":"Reavis HD, Gysler SM, McKenney GB, et al. Norepinephrine induces anoikis resistance in high-grade serous ovarian cancer precursor cells. JCI Insight. 2024;9(5):e170961. 10.1172\/jci.insight.170961.","journal-title":"JCI Insight"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1042734","DOI":"10.3389\/fcell.2022.1042734","article-title":"Fallopian tube secreted protein affects ovarian metabolites in high grade serous ovarian cancer","volume":"10","author":"Bergsten TM","year":"2022","unstructured":"Bergsten TM, Levy SE, Zink KE, et al. Fallopian tube secreted protein affects ovarian metabolites in high grade serous ovarian cancer. Front Cell Dev Biol. 2022;10:1042734. 10.3389\/fcell.2022.1042734.","journal-title":"Front Cell Dev Biol"},{"issue":"6","key":"ref67","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1039\/d1mo00074h","article-title":"Models for measuring metabolic chemical changes in the metastasis of high grade serous ovarian cancer: Fallopian tube, ovary, and omentum","volume":"17","author":"Lusk H","year":"2021","unstructured":"Lusk H, Burdette JE, Sanchez LM. Models for measuring metabolic chemical changes in the metastasis of high grade serous ovarian cancer: Fallopian tube, ovary, and omentum. Mol Omics. 2021;17(6):819\u201332. 10.1039\/d1mo00074h.","journal-title":"Mol Omics"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-9508767\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-9508767\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:37:51Z","timestamp":1784205471000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-9508767\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":67,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-9508767\/v1","relation":{},"subject":[],"published":{"date-parts":[[2026,7,16]]},"subtype":"preprint"}}