P2Y purinergic receptors regulate the growth of human melanomas.
Adenosine 5'-triphosphate is known to function as a potent extracellular messenger producing its effects via a distinct family of cell surface receptors. Different receptor subtypes have been shown to modulate different cellular functions such as proliferation, differentiation and apoptosis. We investigated the functional expression and proliferative action of metabotropic P2Y receptors in human melanoma tissue and cells. Expression of functional P2Y1, P2Y2 and P2Y6 receptor subtypes was established by reverse transcriptase polymerase chain reaction, immunohistochemistry and intracellular calcium measurements using a Fluorometric Imaging Plate Reader. Incubation of A375 melanoma cells with the P2Y1 receptor-selective agonist 2-methylthioadenosine-5-diphosphate caused a decrease in cell number which was dose-dependent, whereas incubation with the P2Y2 receptor agonist uridine triphosphate caused a dose-dependent increase in cell number. The action of extracellular nucleotides on P2Y receptors was shown to mediate the growth of melanomas and the P2Y1 receptor is a putative target for melanoma therapy.
White
Nicholas
N
Autonomic Neuroscience Institute, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
Ryten
Mina
M
Clayton
Elizabeth
E
Butler
Peter
P
Burnstock
Geoffrey
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D016133:Polymerase Chain Reaction; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate