A high-efficiency translational control element with potential for cancer gene therapy.
An active internal ribosome entry sequence (IRES) that efficiently mediates cap (m7pppGN)-independent translation in human carcinoma cells could be an effective device for gene co-transduction in cancer gene therapy. In this study using the cytomegalovirus (CMV) promoter, a remarkable internal translation activity was observed and mediated by the sequence localized to the 183-653 region of 5' NF-kappaB repressor mRNA (NFR183IRES). To test the potential of such sequence for therapeutic application, we carried out in vitro functional assays using the dicistronic constructs that internally expressed human PTEN tumor suppressor. The PTEN expression mediated by NFR183IRES was found to result in growth inhibition of carcinoma cells more effectively than the expression by NFR1IRES that contained the 1-653 region. When compared to the internal translation driven by the picornaviral IRES element of the encephalomyocarditis virus (EMCV) or the foot-and-mouth disease virus (FMDV), NFR183IRES consistently exhibited a higher activity in the human carcinoma cells, HeLa, LNCaP and MCF7. Such high-efficiency translational control element may prove useful for cancer gene therapy.
Wang
Steven I
SI
Case Western Reserve University, Dermatology Department, Cleveland, OH 44106-5028, USA.
Mukhtar
Hasan
H
D020121:5' Untranslated Regions; D015316:Genetic Therapy; D006801:Humans; D016328:NF-kappa B / Q000235:genetics*; D009369:Neoplasms / Q000628:therapy*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics
D020121:5' Untranslated Regions; D016328:NF-kappa B; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human