Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma

doi:10.1111/cas.15440

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/34555

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34555

Title:	Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma
Authors:	Dochi, Hirotomo Kondo, Satoru Murata, Takayuki Fukuyo, Masaki Nanbo, Asuka Wakae, Kousho Jiang, Wen-Ping Hamabe-Horiike, Toshihide Tanaka, Mariko Nishiuchi, Takumi Mizokami, Harue Moriyama-Kita, Makiko Kobayashi, Eiji Hirai, Nobuyuki Komori, Takeshi Ueno, Takayoshi Nakanishi, Yosuke Hatano, Miyako Endo, Kazuhira Sugimoto, Hisashi Wakisaka, Naohiro Juang, Shin-Hun Muramatsu, Masamichi Kaneda, Atsushi Yoshizaki, Tomokazu
Contributors:	Kanazawa University Fujita Health University Chiba University Nagasaki University National Institute of Infectious Diseases (NIID) Department of Pharmacy, Chia Nan University of Pharmacy & Science Kanazawa University China Medical University Taiwan
Keywords:	barr-virus reactivation human breast-cancer gene-expression aromatase infection bzlf1 dna antibodies latent
Date:	2022
Issue Date:	2023-12-11 13:57:38 (UTC+8)
Publisher:	WILEY
Abstract:	Several epidemiological studies have suggested that Epstein-Barr virus (EBV) lytic infection is essential for the development of nasopharyngeal carcinoma (NPC), as the elevation of antibody titers against EBV lytic proteins is a common feature of NPC. Although ZEBRA protein is a key trigger for the initiation of lytic infection, whether its expression affects the prognosis and pathogenesis of NPC remains unclear. In this study, 64 NPC biopsy specimens were analyzed using immunohistochemistry. We found that ZEBRA was significantly associated with a worsening of progression-free survival in NPC (adjusted hazard ratio, 3.58; 95% confidence interval, 1.08-11.87; p = 0.037). Moreover, ZEBRA expression positively correlated with key endocrinological proteins, estrogen receptor alpha, and aromatase. The transcriptional level of ZEBRA is activated by estrogen in an estrogen receptor alpha-dependent manner, resulting in an increase in structural gene expression levels and extracellular virus DNA copy number in NPC cell lines, reminiscent of lytic infection. Interestingly, it did not suppress cellular proliferation or increase apoptosis, in contrast with cells treated with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate, indicating that viral production induced by estrogen is not a cell lytic phenomenon. Our results suggest that intratumoral estrogen overproduced by aromatase could induce ZEBRA expression and EBV reactivation, contributing to the progression of NPC.
Relation:	Cancer Science, v.113, n.8, pp.2862-2877
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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