Abstract:

Objective

To evaluate the effects of nucleoside analogphosphorylation by Dm-dNK（Drosophila melanogaster deoxyribonucleosidekinase）， and the killing effect as a novel suicide geneon in breast cancer cell lines.

Methods

A replication-deficientretroviral'vector that expresses Dm-dNK was created， and the human breast cancer cells MCF7 （ER + ） and MDA-MB-231 （ER- ） were transduced with the recombinant retrovirus.The enzymatic activity and the sensitivity of the untransfected cells and the cells infected with either GFP （green fluorescent protein） vector alone or the pLE-Dm-dNK-GFP to pyrimidine nucleoside analogs araT（1-β-Darabinofuranosylthymine） and araC （1-β-D-arabinofuranosylcytosine） were determined.

Results

It was showed that the Dm-dNK was enzymatically active and that the over-expression of the enzyme in the tested cell lines resulted in an increased sensitivity to the cytosine nucleoside analogs araT and araC.

Conclusions

Dm-dNK can be locally overexpressed in the nuclei of breast cancer cells and it retains enzymatic activity.It may contribute to the development of novel breast cancer treatment strategies.

Key words: Gene therapy, Molecular chemotherapy, Nucleosideanalogs, Nucleoside kinase