Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma.
BZLF1
ZEBRA
estrogen
lytic infection
nasopharyngeal carcinoma
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
revised:
11
05
2022
received:
16
09
2021
accepted:
20
05
2022
pubmed:
29
5
2022
medline:
10
8
2022
entrez:
28
5
2022
Statut:
ppublish
Résumé
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 α, and aromatase. The transcriptional level of ZEBRA is activated by estrogen in an estrogen receptor α-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.
Identifiants
pubmed: 35633182
doi: 10.1111/cas.15440
pmc: PMC9357606
doi:
Substances chimiques
BZLF1 protein, Herpesvirus 4, Human
0
Estrogen Receptor alpha
0
Estrogens
0
Trans-Activators
0
Aromatase
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2862-2877Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 16H05480
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 17H01590
Informations de copyright
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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