title: The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster as a therapeutic suicide gene of breast cancer cells.
abstract: BACKGROUND
  The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) was investigated for its broader substrate specificity and higher catalytic rate as a suicide gene in a combined gene/chemotherapy of cancer.
  
  
  METHODS
  To evaluate the effects of nucleoside analog phosphorylation by Dm-dNK in vitro and in vivo, we generated a replication-deficient retroviral vector expressing Dm-dNK to transduce human breast cancer cells MCF7 (ER+) and MDA-MB-231 (ER-). We further determined the enzymatic activity and the sensitivity of the nontransduced and Dm-dNK-transduced 231/dNK and MCF7/dNK cells to the pyrimidine nucleoside analogs araC and araT.
  
  
  RESULTS
  The data obtained show that Dm-dNK is enzymatically active and its overexpression in the nuclei of breast cancer cells results in an increased sensitivity to the nucleoside analogs araC and araT in vitro. Furthermore, subcutaneously transplanted 231/dNK cells were significantly inhibited after araC treatment, whereas nontransduced cancer cells continued to grow and develop in vivo.
  
  
  CONCLUSIONS
  These results suggest that the Dm-dNK/nucleoside analog system could be a novel therapeutic strategy for treating breast cancer and improving anti-tumor efficacy, as well as for optimizing approaches for suicide gene therapy.
authors.affiliation: Department of Surgical Oncology, Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ma
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhu
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.forename: Huimian
authors.initials: H
authors.lastname: Xu
authors.forename: Magnus
authors.initials: M
authors.lastname: Johansson
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D004331:Drosophila melanogaster / Q000201:enzymology*; D005260:Female; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism / Q000627:therapeutic use*; D012190:Retroviridae; D013379:Substrate Specificity; D014161:Transduction, Genetic
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C020018:deoxyribonucleoside kinases