Item type |
デフォルトアイテムタイプ(フル)(1) |
公開日 |
2021-11-10 |
タイトル |
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タイトル |
Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage |
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言語 |
en |
作成者 |
Uehara, Karina
Tanabe, Yasuka
Hirota, Shintaro
Higa, Saki
Toyoda, Zensei
Kurima, Kiyoto
Kina, Shinichiro
Nakasone, Toshiyuki
Arasaki, Akira
Kinjo, Takao
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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言語 |
ja |
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権利情報 |
© The Author(s). 2021 |
権利情報 |
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言語 |
en |
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権利情報 |
Creative Commons Attribution 4.0 |
権利情報 |
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言語 |
en |
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権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
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権利情報 |
https://creativecommons.org/licenses/by/4.0/ |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Low-risk HPV |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
High-risk HPV |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
EBV LMP-1 |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Co-expression |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Precancerous lesion |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Background:Low-risk human papillomavirus (HPV), such as types 6 and 11, is considered non-oncogenic, but these types have been detected in oral cancer tissue samples, suggesting their possible involvement in oral carcinogenesis. Because double infection of high-risk HPV and Epstein-Barr virus (EBV) is known to be involved in oral carcinogenesis, we hypothesized that low-risk HPV and EBV co-infection can transform the oral cells. To verify our hypothesis, we evaluated the transformation activity of cell lines expressing both low-risk HPV E6/E7 and EBV LMP-1.\nMethods:We transduced HPV6, 11 and 16 E6/E7 genes and EBV LMP-1 gene into primary mouse embryonic fibroblasts. The cell lines were examined for indices of transformation activity such as proliferation, induction of DNA damage, resistance to apoptosis, anchorage-independent growth, and tumor formation in nude mice. To evaluate the signaling pathways involved in transformation, NF-κB and p53 activities were analyzed. We also assessed adhesion signaling molecules associated with anchorage-independent growth such as MMP-2, paxillin and Cat-1.\nResults:Co-expression of low-risk HPV6 E6 and EBV LMP-1 showed increased cell proliferation, elevated NF-κB activity and reduced p53 induction. Moreover, co-expression of low-risk HPV6 E6 and EBV LMP-1 induced DNA damage, escaped from apoptosis under genotoxic condition and suppression of DNA damage response (DDR). Co-expression of low-risk HPV11 E6/E7 and EBV LMP-1 demonstrated similar results. However, it led to no malignant characteristics such as anchorage-independent growth, invasiveness and tumor formation in nude mice. Compared with the cells co-expressing high-risk HPV16 E6 and EBV LMP-1 that induce transformation, co-expression of low-risk HPV6 E6 and EBV LMP-1 was associated with low MMP-2, paxillin and Cat-1 expression.\nConclusions:The co-expression of low-risk HPV E6/E7 and EBV LMP-1 does not induce malignant transformation, but it allows accumulation of somatic mutations secondary to increased DNA damage and suppression of DDR. Thus, double infection of low-risk HPV and EBV could lead to precancerous lesions. |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
論文 |
出版者 |
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言語 |
en |
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出版者 |
Springer Nature |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ |
journal article |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
識別子 |
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識別子 |
http://hdl.handle.net/20.500.12000/49986 |
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識別子タイプ |
HDL |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1186/s12885-021-08397-0 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1186/s12885-021-08397-0 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1471-2407 |
収録物名 |
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言語 |
en |
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収録物名 |
BMC Cancer |
書誌情報 |
巻 21,
号 1,
発行日 2021-06-10
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