Selective killing of cancer cells based on translational control of a suicide gene.
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.
DeFatta
Robert J
RJ
Department of Biochemistry and Molecular Biology and the Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
Li
Yuan
Y
De Benedetti
Arrigo
A
D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics* / Q000378:metabolism; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger; D013937:Thymidine Kinase; D015774:Ganciclovir