Characterization of phosphodiesterase 2A in human malignant melanoma PMP cells

• Material Type: 博士論文
• Title: Characterization of phosphodiesterase 2A in human malignant melanoma PMP cells
• Author/Editor: MORITA, HIROSHI
• Author Heading: MORITA, HIROSHI
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2013-01-01
• Publication Date (W3CDTF): 2013-01-01
• Degree grantor/type: 三重大学
• Date Granted: 2013-07-17
• Date Granted (W3CDTF): 2013-07-17
• Dissertation Number: 甲医学第1632号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医学第1632号
• Text Language Code: eng
• Alias of Author: モリタ, ヒロシ; 森田, 寛
• Subject Heading: malignant melanoma; phosphodiesterase 2A; cell cycle
• Target Audience: 一般
• Note (General): application/pdf; The prognosis for malignant melanoma is poor; therefore, new diagnostic methods and treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of 21 phosphodiesterases, which are divided into 11 families (PDE1-PDE11). PDE2 hydrolyzes cyclic AMP (cAMP) and cyclic GMP (cGMP), and its binding to cGMP enhances the hydrolysis of cAMP. We previously reported the expression of PDE1, PDE3 and PDE5 in human malignant melanoma cells. However, the expression of PDE2 in these cells has not been investigated. Herein, we examined the expression of PDE2A and its role in human oral malignant melanoma PMP cells. Sequencing of RT-PCR products revealed that PDE2A2 was the only variant expressed in PMP cells. Four point mutations were detected; one missense mutation at nucleotide position 734 (from C to T) resulted in the substitution of threonine with isoleucine at amino acid position 214. The other three were silent mutations. An in vitro migration assay and a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay revealed that suppressing PDE2 activity with its specific inhibitor, erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA), had no impact on cell motility or apoptosis. Furthermore, the cytotoxicity of EHNA, assessed using a trypan blue exclusion assay, was negligible. On the other hand, assessment of cell proliferation by BrdU incorporation and cell cycle analysis by flow cytometry revealed that EHNA treatment inhibited DNA synthesis and increased the percentage of G2/M-arrested cells. Furthermore, cyclin A mRNA expression was downregulated, while cyclin E mRNA expression was upregulated in EHNA-treated cells. Our results demonstrated that the PDE2A2 variant carrying point mutations is expressed in PMP cells and may affect cell cycle progression by modulating cyclin A expression. Thus, PDE2A2 is a possible new molecular target for the treatment of malignant melanoma.; 本文 / Department of Oral and Maxillofacial Surgery, Department of Clinical Sciences,Medical Life Science, Mie University Graduate School of Medicine; 10p; http://www.spandidos-publications.com/10.3892/or.2013.2260
• DOI: info:doi/10.3892/or.2013.2260; https://doi.org/info:doi/10.3892/or.2013.2260
• Persistent ID (NDL): info:ndljp/pid/8951815; https://dl.ndl.go.jp/pid/8951815
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Available (W3CDTF): 2015-03-03
• Date Accepted (W3CDTF): 2015-02-03T05:25:05+09:00
• Date Created (W3CDTF): 2017-02-18
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Related Material (URI): http://www.spandidos-publications.com/10.3892/or.2013.2260
• Periodical Title (URI): http://hdl.handle.net/10076/13987; https://mie-u.repo.nii.ac.jp/records/7810
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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