Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis

Stav Sapoznik; Keren Bahar-Shany; Hadar Brand; Yishay Pinto; Orshay Gabay; Efrat Glick-Saar; Chen Dor; Oranit Zadok; Iris Barshack; Adi Zundelevich; Einav Nili Gal-Yam; Yuval Yung; Ariel Hourvitz; Jacob Korach; Mario Beiner; Jasmine Jacob; Erez Y. Levanon; Michal Barak; Sarit Aviel-Ronen; Keren Levanon

doi:10.1016/j.neo.2015.12.003

Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis

Stav Sapoznik, Keren Bahar-Shany, Hadar Brand, Yishay Pinto, Orshay Gabay, Efrat Glick-Saar, Chen Dor, Oranit Zadok, Iris Barshack, Adi Zundelevich, Einav Nili Gal-Yam, Yuval Yung, Ariel Hourvitz, Jacob Korach, Mario Beiner, Jasmine Jacob, Erez Y. Levanon, Michal Barak, Sarit Aviel-Ronen, Keren Levanon

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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.

Original language	English
Pages (from-to)	90-99
Number of pages	10
Journal	Neoplasia
Volume	18
Issue number	2
DOIs	https://doi.org/10.1016/j.neo.2015.12.003
State	Published - Feb 2016

Bibliographical note

Funding Information:
This research was supported by research grants from the Israel Cancer Research Fund Clinical Research Career Development Award, the Israeli Ministry of Health Chief Scientist Research Grant, The Israel Cancer Association, and the Chaim Sheba Medical Center Dr. Pinchas Bornstein Talpiot Medical Leadership Program.

Publisher Copyright:
© 2015 The Authors.

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Sapoznik, S., Bahar-Shany, K., Brand, H., Pinto, Y., Gabay, O., Glick-Saar, E., Dor, C., Zadok, O., Barshack, I., Zundelevich, A., Gal-Yam, E. N., Yung, Y., Hourvitz, A., Korach, J., Beiner, M., Jacob, J., Levanon, E. Y., Barak, M., Aviel-Ronen, S., & Levanon, K. (2016). Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis. Neoplasia, 18(2), 90-99. https://doi.org/10.1016/j.neo.2015.12.003

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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.",

author = "Stav Sapoznik and Keren Bahar-Shany and Hadar Brand and Yishay Pinto and Orshay Gabay and Efrat Glick-Saar and Chen Dor and Oranit Zadok and Iris Barshack and Adi Zundelevich and Gal-Yam, {Einav Nili} and Yuval Yung and Ariel Hourvitz and Jacob Korach and Mario Beiner and Jasmine Jacob and Levanon, {Erez Y.} and Michal Barak and Sarit Aviel-Ronen and Keren Levanon",

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Sapoznik, S, Bahar-Shany, K, Brand, H, Pinto, Y, Gabay, O, Glick-Saar, E, Dor, C, Zadok, O, Barshack, I, Zundelevich, A, Gal-Yam, EN, Yung, Y, Hourvitz, A, Korach, J, Beiner, M, Jacob, J, Levanon, EY, Barak, M, Aviel-Ronen, S & Levanon, K 2016, 'Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis', Neoplasia, vol. 18, no. 2, pp. 90-99. https://doi.org/10.1016/j.neo.2015.12.003

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AU - Pinto, Yishay

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AU - Zadok, Oranit

AU - Barshack, Iris

AU - Zundelevich, Adi

AU - Gal-Yam, Einav Nili

AU - Yung, Yuval

AU - Hourvitz, Ariel

AU - Korach, Jacob

AU - Beiner, Mario

AU - Jacob, Jasmine

AU - Levanon, Erez Y.

AU - Barak, Michal

AU - Aviel-Ronen, Sarit

AU - Levanon, Keren

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Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis

Abstract

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