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| 標題: | Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma |
| 作者: | 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 |
| 貢獻者: | 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 |
| 關鍵字: | barr-virus reactivation
human breast-cancer
gene-expression
aromatase
infection
bzlf1
dna
antibodies
latent |
| 日期: | 2022 |
| 上傳時間: | 2023-12-11 13:57:38 (UTC+8) |
| 出版者: | WILEY |
| 摘要: | 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. |
| 關聯: | Cancer Science, v.113, n.8, pp.2862-2877 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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