A cancer gene therapy approach through translational control of a suicide gene.
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.
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.
Chervenak
Robert P
RP
De Benedetti
Arrigo
A
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
D020121:5' Untranslated Regions; D039561:Eukaryotic Initiation Factor-4E; D008081:Liposomes; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D013937:Thymidine Kinase