title: Nucleoside Analog Activity in Malignant Melanoma Cell Lines.
abstract: Mitochondrial deoxyguanosine kinase (dGK), is an enzyme responsible for activation of nucleoside analogs (NAs) to phosphorylated compounds which exert profound cytotoxicity, especially in hematological malignancies. Screening malignant melanoma cell lines against NAs revealed high sensitivity to several of them. This was believed to be due to the high levels of dGK expression in these cells. Downregulation of dGK in the melanoma cell line RaH5 using siRNA did not cause resistance to NAs as expected, but instead cells became more sensitive. This was probably partly due to the increased activity of another mitochondrial enzyme, thymidine kinase 2, seen in transfected cells.
authors.affiliation: a Centre for Biomedical Resources , Linköping University , Linköping , Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Fyrberg
authors.forename: Kourosh
authors.initials: K
authors.lastname: Lotfi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003842:Deoxycytidine Kinase / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D009705:Nucleosides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D003842:Deoxycytidine Kinase
keywords: Deoxyguanosine kinase; RNAi; leukemia; melanoma; nucleoside analog