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  1. 教員研究業績
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ZO-2 Suppresses Cell Migration Mediated by a Reduction in Matrix Metalloproteinase 2 in Claudin-18-Expressing Lung Adenocarcinoma A549 Cells.

https://gifu-pu.repo.nii.ac.jp/records/13471
https://gifu-pu.repo.nii.ac.jp/records/13471
a40c43b2-2f70-4ef6-8fd8-e6b7b90f6ca6
Item type 研究室原著論文(1)
公開日 2019-03-05
タイトル
タイトル ZO-2 Suppresses Cell Migration Mediated by a Reduction in Matrix Metalloproteinase 2 in Claudin-18-Expressing Lung Adenocarcinoma A549 Cells.
言語 en
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
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アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
item_3_textarea_2
値 Abnormal expression of the tight junctional components claudins (CLDNs) is observed in various malignant tissues. We reported recently that CLDN18 expression is down-regulated in human lung adenocarcinoma tissues. In the present study, we investigated the biological functions of CLDN18 using lung adenocarcinoma A549 cells. Microarray analysis showed that CLDN18 increases zonula occludens (ZO)-2 expression in A549 cells. The ectopic expression of CLDN18 increased nuclear ZO-2 levels, which were inhibited by N-[2-[[3-(4-bromophenyl)-2-propen-1-yl]amino]ethyl]5-isoquinolinesulfonamide (H-89), a nonspecific protein kinase A (PKA) inhibitor, but not by a PKA inhibitor 14-22 amide. In addition, dibutyryl cyclic adenosine monophosphate, an analogue of PKA, did not increase ZO-2 levels. These results suggest that H-89 sensitive factors without PKA are involved in the CLDN18-induced elevation of ZO-2. The cell cycle was affected by neither ZO-2 knockdown in CLDN18-expresssing A549 (CLDN18/A549) cells nor ZO-2 overexpression in A549 cells, suggesting that ZO-2 does not play an important role in the regulation of cell proliferation. The introduction of ZO-2 small interfering RNA (siRNA) into CLDN18/A549 cells increased migration, the expression and activity of matrix metalloproteinase 2 (MMP2), and the reporter activity of an MMP2 promoter construct. Furthermore, H-89 enhanced both mRNA levels and reporter activity of MMP2 in CLDN18/A549 cells. These results suggested that a reduction in CLDN18-dependent ZO-2 expression enhances MMP2 expression in lung adenocarcinoma cells, resulting in the promotion of the cell migration. CLDN18 may be a novel marker for metastasis in lung adenocarcinoma.
bibliographic_information en : Biological & pharmaceutical bulletin

巻 42, 号 2, p. 247-254, ページ数 8, 発行日 2019-03
item_3_text_4
値 10.1248/bpb.b18-00670
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2019, ZO-2 Suppresses Cell Migration Mediated by a Reduction in Matrix Metalloproteinase 2 in Claudin-18-Expressing Lung Adenocarcinoma A549 Cells.: 247–254 p.

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