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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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