Cell cycle arrest and apoptosis induced by SART-1 gene transduction

Anticancer Res. 2005 May-Jun;25(3B):1983-90.

Abstract

The biological function of the SART-1 gene product is demonstrated and its potential as a target for cancer gene therapy is discussed.

Materials and methods: The SART-1 gene was transduced by a recombinant adenovirus vector and its expression was promoted by a CMV promoter.

Results: The transduction efficiency by recombinant adenoviruses in A549 and MCF-7 cells was determined using a vector expressing luciferase, which showed high expression in the cells. Cell count analysis using Trypan-Blue dye exclusion showed that SART-1 gene transduction inhibited cell growth. Flow cytometry analysis suggested that SART-1 gene transduction induced cell cycle arrest followed by apoptosis. Western blot analysis confirmed that the apoptosis pathway was activated by SART-1 gene transduction.

Conclusion: These results show that SART-1 gene transduction induces cell cycle arrest leading to apoptosis and suggest the possibility of gene therapy against cancer. In addition, SART-1 is known to be a tumor antigen in a range of cancers recognized by T cells, thus a potential strategy would be the combination of suicide gene therapy with immuno-gene therapy.

MeSH terms

  • Adenoviridae / genetics
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / physiology
  • Apoptosis / genetics*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / genetics
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Flow Cytometry
  • Genetic Therapy / methods
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Oligopeptides / genetics
  • Ribonucleoproteins, Small Nuclear / genetics*
  • Ribonucleoproteins, Small Nuclear / physiology
  • Transduction, Genetic

Substances

  • Antigens, Neoplasm
  • Oligopeptides
  • Ribonucleoproteins, Small Nuclear
  • SART1 protein, human
  • arginyl-glycyl-aspartic acid