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001-es BibID:BIBFORM125834
Első szerző:Tímár József
Cím:Genomics of calcium signaling in human melanoma / József Tímár, Erzsebet Raso, Tamás Deli, László Csernoch
Dátum:2006
ISSN:0008-5472 1538-7445
Megjegyzések:Melanoma is one of the most aggressive human cancer which can colonize the host from a very small primary. On the other hand, melanoma is characterized by an apoptosis-resistant pheno-genotype resulting in resistance to chemotherapy. We have used DNA microarray technology to profile human melanoma compared to benign tumor (nevi) and metastatic variants to non-metastatic ones to reveal genetic background of its geno-phenotype. For this purpose we have used 3 genetically distinct human melanoma cell lines grown in vitro and in vivo. Data indicated that during progression of melanocytes toward melanoma several genes involved in calcium signaling were found to be upregulated including the ryanodin receptor-2 (RYR2), P2X7R and sorcin. During the metastatic progression, beside further upregulation of the P2X7R receptor another set of calcium-signaling genes were found to be upregulated such as T-type Ca-channel-1, sorting nexin and calneuron-1. Functional studies revealed that the RYR2 is not involved directly in Ca-signaling which is predominantly mediated by the purinergic P2X7R receptor. Activation of the RYR2 resulted in stimulation of cell proliferation, while activation of P2X7R by ATP inhibited apoptosis. On the other hand, P2X7R inhibition by Zn++ induced strong inhibition of cell proliferation of human melanoma cell lines partialy mediated by induction of apoptosis. These studies provide the first evidences for the crucial role for calcium signaling in the progression of human melanoma and may provide novel therapeutic targets.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
genomics
calcium signaling
human melanoma
ryanodine receptor
P2X7 purinergic receptor
Megjelenés:Cancer Research. - 66 : Supplement 8 (2006), p. 982. -
További szerzők:Rásó Erzsébet Deli Tamás (1979-) (szülész-nőgyógyász, endokrinológus szakorvos) Csernoch László (1961-) (élettanász)
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