title: Utilization of Rad51C promoter for transcriptional targeting of cancer cells.
abstract: Cancer therapy that specifically targets malignant cells with minimal or no toxicity to normal tissue has been a long-standing goal of cancer research. Rad51 expression is elevated in a wide range of cancers and Rad51 promoter has been used to transcriptionally target tumor cells, however, a large size of Rad51 promoter limits its application for gene therapy. To identify novel tumor-specific promoters, we examined expression levels of Rad51 paralogs, Rad51B, Rad51C, and Rad51D as well as Rad52 in a panel of normal and tumor cell lines. We found that Rad51C is significantly overexpressed in cancer cells. The expression was up-regulated by approximately 6-fold at the mRNA level and 9-fold at the protein level. Interestingly, the 2064 bp long Rad51C promoter fragment was approximately 300-fold higher in cancer cells than in normal cells. A construct containing Rad51C promoter driving diphtheria toxin A efficiently killed several types of cancer cells with very mild effect to normal cells. These results underscore the potential of targeting the homologous recombination pathway in cancer cells and provide a proof of principle that the Rad51C promoter fragment can be used to transcriptionally target cancer cells.
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiao
authors.initials: X
authors.lastname: Tian
authors.forename: Andrei
authors.initials: A
authors.lastname: Seluanov
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Mao
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004167:Diphtheria Toxin / Q000235:genetics*; D050939:Gene Fusion; D006801:Humans; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D004167:Diphtheria Toxin; D010446:Peptide Fragments; C413002:RAD51B protein, human; C448305:RAD51C protein, human; C112629:RAD51D protein, human; C497194:RAD52 protein, human; D012333:RNA, Messenger; D051721:Rad52 DNA Repair and Recombination Protein; C029795:diphtheria toxin fragment A; D049409:Luciferases, Firefly
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