title: Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis.
abstract: In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs) has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID) as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection.
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Stav
authors.initials: S
authors.lastname: Sapoznik
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Bahar-Shany
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Brand
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Yishay
authors.initials: Y
authors.lastname: Pinto
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Orshay
authors.initials: O
authors.lastname: Gabay
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Glick-Saar
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Dor
authors.affiliation: Department of Pathology, Chaim Sheba Medical Center, Ramat-Gan 52621, Israel.
authors.forename: Oranit
authors.initials: O
authors.lastname: Zadok
authors.affiliation: Department of Pathology, Chaim Sheba Medical Center, Ramat-Gan 52621, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Zundelevich
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel; The Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Einav Nili
authors.initials: EN
authors.lastname: Gal-Yam
authors.affiliation: IVF Unit and Reproduction Lab, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat-Gan, 52621, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yung
authors.affiliation: IVF Unit and Reproduction Lab, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat-Gan, 52621, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Hourvitz
authors.affiliation: Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Korach
authors.affiliation: Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Mario
authors.initials: M
authors.lastname: Beiner
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Erez Y
authors.initials: EY
authors.lastname: Levanon
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Barak
authors.affiliation: Department of Pathology, Chaim Sheba Medical Center, Ramat-Gan 52621, Israel; The Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Aviel-Ronen
authors.affiliation: Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Israel; The Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Ramat Gan, 52621, Israel. Electronic address: Keren.Levanon@Sheba.health.gov.il.
authors.forename: Keren
authors.initials: K
authors.lastname: Levanon
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005187:Fallopian Tubes / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010060:Ovulation / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase