Characterization of phosphodiesterase 1 in human malignant melanoma cell lines.
BACKGROUND
Differentiation-inducing factor 1 [DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-one] from Dictyostelium discoideum exhibits antiproliferative activity in mammalian cells. We have previously shown that phosphodiesterase 1 (PDE1) is a pharmacological target of DIF-1, but there are no reports of PDE1 in human malignant melanoma cells. Therefore, we characterized PDE1 in human malignant melanoma MAA cells.


METHODS
PDE1 mRNA expression was investigated in MAA cells. The full open reading frames for human PDE1C1 and PDE1C3 were cloned. Cell growth was determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay.


RESULTS
PDE1C mRNA expression was detected in MAA cells. The nucleotide sequence of PDE1C1 was identical to that of human PDE1C1, previously published. At nucleotide 2246 in PDE1C3, A was replaced by G, but this did not change the encoded amino acid. Cell growth was inhibited by the PDE1 inhibitor vinpocetin.


CONCLUSIONS
PDE1C mRNA is expressed and may play an important role in human malignant melanoma MAA cells.
Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Japan. skasumi@clin.medic.mie-u.ac.jp
Kasumi
K
Shimizu
Taku
T
Murata
Yoshihiro
Y
Watanabe
Chu
C
Sato
Hiroshi
H
Morita
Toshiro
T
Tagawa
D000959:Antihypertensive Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014748:Vinca Alkaloids / Q000494:pharmacology
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D014748:Vinca Alkaloids; C013983:vinpocetine; D000242:Cyclic AMP; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517272:PDE1C protein, human