{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:01:38Z","timestamp":1773363698986,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-14-1-0280"],"award-info":[{"award-number":["W81XWH-14-1-0280"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008035","name":"Harvard Stem Cell Institute","doi-asserted-by":"publisher","award":["DP-0164-17-00"],"award-info":[{"award-number":["DP-0164-17-00"]}],"id":[{"id":"10.13039\/100008035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005292","name":"Brigham and Women's Hospital","doi-asserted-by":"publisher","award":["Sundry Fund"],"award-info":[{"award-number":["Sundry Fund"]}],"id":[{"id":"10.13039\/100005292","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ovarian and uterine cancers are the most prevalent types of gynecological malignancies originating from mesothelial and\/or M\u00fcllerian-derived epithelial cells. Recent genomic studies have identified common mutations in them that affect signaling pathways such as p53, PTEN\/PI3K, RAS, and WNT pathways. However, how these mutations and their corresponding deregulated pathways affect gynecological cancer development from their cells-of-origin remains largely elusive. To address this, we performed the intrabursal injection of Cre-expressing adenovirus under the control of Krt8 promoter (Ad-K8-Cre) to mice carrying combinations of various conditional alleles for cancer genes. We found that Ad-K8-Cre specifically targeted mesothelial cells, including ovarian surface epithelial (OSE) cells (mainly the LGR5+ subset of OSE cells) and mesothelial cells lining the fallopian tube (FT) serosa; the injected Ad-K8-Cre also targeted M\u00fcllerian-derived epithelial cells, including FT epithelial cells and uterine endometrial epithelial cells. The loss of p53 may preferentially affect M\u00fcllerian-derived epithelial cells, leading to the development of uterine and ovarian malignancies, whereas PTEN-loss may preferentially affect mesothelial cells, leading to the development of ovarian endometrioid malignancies (upon KRAS-activation or APC-loss) or adenoma on the FT surface (upon DICER-loss). Overall, our data suggest that different Krt8+ mesothelial and epithelial cell types in the female reproductive system may have different sensitivities toward oncogenic mutations and, as a result, oncogenic events may dominantly determine the locations and types of the gynecological malignancies developed from them.<\/jats:p>","DOI":"10.3390\/cancers14030841","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T01:03:40Z","timestamp":1644368620000},"page":"841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oncogenic Events Dictate the Types and Locations of Gynecological Malignancies Originating from Krt8+ Mesothelial and M\u00fcllerian-Derived Epithelial Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Eun-Sil","family":"Park","sequence":"first","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxi","family":"Xiang","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roderick T.","family":"Bronson","sequence":"additional","affiliation":[{"name":"Rodent Histopathology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-0885","authenticated-orcid":false,"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ejca.2017.10.030","article-title":"No improvement in long-term survival for epithelial ovarian cancer patients: A population-based study between 1989 and 2014 in the Netherlands","volume":"88","author":"Timmermans","year":"2018","journal-title":"Eur. 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