title: A cancer gene therapy approach through translational control of a suicide gene.
abstract: The translation initiation factor eIF4E is elevated in most solid tumors resulting in translation of mRNAs that are normally repressed by their structured 5' untranslated region. We have introduced a translational repressor element in a vector (BK-UTK) designed to express herpes thymidine kinase (HTK). This and a control vector (BK-TK) were used to treat experimental tumors of a murine breast cancer line. Both vectors were equally effective in reducing subcutaneous tumors and lung metastases following ganciclovir administration. However, the BK-TK vector was found to be highly toxic, resulting in severe weight loss, degeneration of various organs, and early death of mice following systemic vector delivery, whereas the BK-UTK increased mean survival without toxicity.
authors.affiliation: Department of Biochemistry and Molecular Biology and the Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DeFatta
authors.forename: Robert P
authors.initials: RP
authors.lastname: Chervenak
authors.forename: Arrigo
authors.initials: A
authors.lastname: De Benedetti
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D039561:Eukaryotic Initiation Factor-4E; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009362:Neoplasm Metastasis; D010448:Peptide Initiation Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D039561:Eukaryotic Initiation Factor-4E; D008081:Liposomes; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D013937:Thymidine Kinase