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

被引：22

作者：

Sapoznik, Stav ^{[1
]}

Bahar-Shany, Keren ^{[1
]}

Brand, Hadar ^{[1
,2
]}

Pinto, Yishay ^{[3
]}

Gabay, Orshay ^{[3
]}

Glick-Saar, Efrat ^{[1
]}

Dor, Chen ^{[1
]}

Zadok, Oranit ^{[4
]}

Barshack, Iris ^{[4
]}

Zundelevich, Adi ^{[1
]}

Gal-Yam, Einav Nili ^{[1
,5
]}

Yung, Yuval ^{[6
,7
]}

Hourvitz, Ariel ^{[6
,7
]}

Korach, Jacob ^{[8
]}

Beiner, Mario ^{[8
]}

Jacob, Jasmine ^{[1
]}

Levanon, Erez Y. ^{[3
]}

Barak, Michal ^{[3
]}

Aviel-Ronen, Sarit ^{[4
,5
]}

Levanon, Keren ^{[1
,2
,5
]}

机构：

[1] Chaim Sheba Med Ctr, Sheba Canc Res Ctr, IL-52621 Ramat Gan, Israel

[2] Tel Aviv Univ, Sackler Fac Med, IL-69978 Ramat Aviv, Israel

[3] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel

[4] Chaim Sheba Med Ctr, Dept Pathol, IL-52621 Ramat Gan, Israel

[5] Chaim Sheba Med Ctr, Talpiot Med Leadership Program, IL-52621 Ramat Gan, Israel

[6] Chaim Sheba Med Ctr, Dept Obstet & Gynecol, IVF Unit, IL-52621 Ramat Gan, Israel

[7] Chaim Sheba Med Ctr, Dept Obstet & Gynecol, Reprod Lab, IL-52621 Ramat Gan, Israel

[8] Chaim Sheba Med Ctr, Dept Gynecol Oncol, IL-52621 Ramat Gan, Israel

来源：

NEOPLASIA | 2016年 / 18卷 / 02期

关键词：

HELICOBACTER-PYLORI INFECTION; B-CELL LYMPHOMA; FOLLICULAR-FLUID; FALLOPIAN-TUBE; OVARIAN CARCINOGENESIS; SOMATIC HYPERMUTATION; MUTATIONAL PROCESSES; INCESSANT OVULATION; GASTRIC EPITHELIUM; DNA DEMETHYLATION;

D O I：

10.1016/j.neo.2015.12.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：90 / 99

页数：10

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