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 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.
Hébrard
Claire
C
INSERM U590, Laboratoire de Cytologie Analytique, Faculte de Medecine Rockefeller, Universite Claude Bernard Lyon I, Lyon, France.
Cros-Perrial
Emeline
E
Clausen
Anders Ranegaard
AR
Dumontet
Charles
C
Piskur
Jure
J
Jordheim
Lars Petter
LP
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001419:Bacteria / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D041722:Genes, Transgenic, Suicide / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020128:Inhibitory Concentration 50; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D017853:Phosphotransferases (Alcohol Group Acceptor); C020018:deoxyribonucleoside kinases; D000093542:Gemcitabine