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Characterization of phosphodiesterase 2A in human malignant melanoma PMP cells
http://hdl.handle.net/10076/13987
http://hdl.handle.net/10076/13987e21129b4-e3ea-48e6-b750-8503bfba8845
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2013DM001.pdf (929.2 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2014-08-21 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Characterization of phosphodiesterase 2A in human malignant melanoma PMP cells | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | malignant melanoma | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | phosphodiesterase 2A | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | cell cycle | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
森田, 寛
× 森田, 寛
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | 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. | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 本文 / Department of Oral and Maxillofacial Surgery, Department of Clinical Sciences, Medical Life Science, Mie University Graduate School of Medicine |
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| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 10p | |||||||||||
| 書誌情報 |
発行日 2013-01-01 |
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| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.3892/or.2013.2260 | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 三重大学 | |||||||||||
| 出版者（ヨミ） | ||||||||||||
| 値 | ミエダイガク | |||||||||||
| 関係URI | ||||||||||||
| 関連名称 | http://www.spandidos-publications.com/10.3892/or.2013.2260 | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 14101 | |||||||||||
| 学位授与機関名 | 三重大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2013-07-17 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲医学第1632号 | |||||||||||
| ノート | ||||||||||||
| 値 | Oncology Reports, 29巻, pp. 1275-1284, 2013, ISSN: 1021-335Xに掲載 | |||||||||||
| 資源タイプ（三重大） | ||||||||||||
| 値 | Doctoral Dissertation / 博士論文 | |||||||||||
