Bacterial Deoxyribonucleoside Kinases are Poor Suicide Genes in Mammalian Cells

Transfer of deoxyribonucleoside kinases (dNKs) into cancer cells increases the activity of cytotoxic nucleoside analogues. It has been shown that bacterial dNKs, when introduced into Escherichia coli, sensitize this bacterium toward nucleoside analogues. We studied the possibility of using bacterial...

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Bibliographic Details
Published in:Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2009-11, Vol.28 (11-12), p.1068-1075
Main Authors: Hébrard, Claire, Cros-Perrial, Emeline, Clausen, Anders Ranegaard, Dumontet, Charles, Piškur, Jure, Jordheim, Lars Petter
Format: Article
Language:English
Subjects:
Animals
Antimetabolites, Antineoplastic - pharmacology
Bacteria
Bacteria - enzymology
Bacteria - genetics
Biologi
Biological Sciences
cancer
Cell Line, Tumor
Deoxycytidine - analogs & derivatives
Deoxycytidine - pharmacology
Deoxyribonucleoside kinases
gemcitabine
gene therapy
Genes, Transgenic, Suicide - genetics
Genes, Transgenic, Suicide - physiology
Humans
Inhibitory Concentration 50
Natural Sciences
Naturvetenskap
Phosphotransferases (Alcohol Group Acceptor) - genetics
Phosphotransferases (Alcohol Group Acceptor) - metabolism
resistance
suicide gene
Transfection
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Summary:Transfer of deoxyribonucleoside kinases (dNKs) into cancer cells increases the activity of cytotoxic nucleoside analogues. It has been shown that bacterial dNKs, when introduced into Escherichia coli, sensitize this bacterium toward nucleoside analogues. We studied the possibility of using bacterial dNKs, for example deoxyadenosine kinases (dAKs), to sensitize human cancer cells to gemcitabine. Stable and transient transfections of bacterial dNKs into human cells showed that these were much less active than human and fruitfly dNKs. The fusion of dAK from Bacillus cereus to the green fluorescent protein induced a modest sensitization. Apparently, bacterial dNKs did not get properly expressed or are unstable in the mammalian cell.
ISSN:1525-7770
1532-2335
DOI:10.1080/15257770903368393