Selective killing of cancer cells based on translational control of a suicide gene

Cancer Gene Ther. 2002 Jul;9(7):573-8. doi: 10.1038/sj.cgt.7700468.

Abstract

The translation initiation factor, eIF4E, is commonly overexpressed in solid tumors. This elevation allows for efficient translation of mRNA that are normally repressed by their 5' untranslated region, many of which encode growth-promoting proteins. This property was exploited to modulate the synthesis of HTK at the translational level to selectively kill cancer cells. Various breast cancer cell lines can efficiently synthesize HTK from the translationally regulated mRNA, whereas normal cells cannot. Accordingly, only cancer cells were killed at low concentrations of ganciclovir. By altering the expression of eIF4E, it was possible to modulate the sensitivity of various cell lines to ganciclovir.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / pharmacology
  • Blotting, Western
  • Breast Neoplasms / metabolism
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Eukaryotic Initiation Factor-4E / genetics*
  • Eukaryotic Initiation Factor-4E / metabolism
  • Ganciclovir / pharmacology
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Phenotype
  • Plasmids / metabolism
  • Protein Biosynthesis*
  • RNA, Messenger / metabolism
  • Thymidine Kinase / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antiviral Agents
  • Eukaryotic Initiation Factor-4E
  • RNA, Messenger
  • Thymidine Kinase
  • Ganciclovir