title: Characterization of phosphodiesterase 2A in human malignant melanoma             PMP cells.
abstract: 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.
authors: Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan. pengin@clin.medic.mie-u.ac.jp
authors: Hiroshi
authors: H
authors: Morita
authors: Taku
authors: T
authors: Murata
authors: Kasumi
authors: K
authors: Shimizu
authors: Kenya
authors: K
authors: Okumura
authors: Madoka
authors: M
authors: Inui
authors: Toshiro
authors: T
authors: Tagawa
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009154:Mutation
chemical_list: D019925:Cyclin A; C010192:9-(2-hydroxy-3-nonyl)adenine; D004247:DNA; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D000225:Adenine
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