title: hTERTandBIRC5gene promoters for cancer gene therapy: A comparative study.
abstract: Human telomerase reverse transcriptase (hTERT) and survivin (BIRC5) gene promoters are frequently used for transcriptional targeting of tumor cells, yet there is no comprehensive comparative analysis allowing rational choice of a promoter for a particular therapy. In the current study, the transcriptional activity ofhTERT, humanBIRC5and mouse Birc5 promoters and their modifications were compared in 10 human cancer cell lines using the luciferase reporter gene activity assay. The results revealed thatBIRC5- andhTERT-based promoters had strikingly different cell specificities with comparable activities in only 40% of cell lines. Importantly, relativehTERTandBIRC5transcript abundance cannot be used to predict the most potent promoter. Among thehTERT-based promoters that were assessed, modification with the minimal cytomegalovirus promoter generally resulted in the most potent activity. MouseBirc5and modified humanBIRC5promoters were superior to the unmodified human survivin promoter; however, their tumor specificities must be investigated further. In summary, the present results emphasize the desirability for construction of more universal tumor-specific promoters to efficiently target a wide spectrum of tumor cells.
authors.affiliation: Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Shepelev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Kopantzev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Vinogradova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia; Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia.
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Sverdlov
authors.affiliation: Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Korobko
keywords: cancer gene therapy; comparative study; hTERT promoter; survivin/BIRC5 promoter; tumor-specific transcription