title: Cancer specificity of promoters of the genes controlling cell proliferation.
abstract: Violation of proliferation control is a common feature of cancer cells. We put forward the hypothesis that promoters of genes involved in the control of cell proliferation should possess intrinsic cancer specific activity. We cloned promoter regions of CDC6, POLD1, CKS1B, MCM2, and PLK1 genes into pGL3 reporter vector and studied their ability to drive heterologous gene expression in transfected cancer cells of different origin and in normal human fibroblasts. Each promoter was cloned in short (335-800 bp) and long (up to 2.3 kb) variants to cover probable location of core and whole promoter regulatory elements. Cloned promoters were significantly more active in cancer cells than in normal fibroblasts that may indicate their cancer specificity. Both versions of CDC6 promoters were shown to be most active while the activities of others were close to that of BIRC5 gene (survivin) gene promoter. Long and short variants of each cloned promoter demonstrated very similar cancer specificity with the exception of PLK1-long promoter that was substantially more specific than its short variant and other promoters under study. The data indicate that most of the important cis-regulatory transcription elements responsible for intrinsic cancer specificity are located in short variants of the promoters under study. CDC6 short promoter may serve as a promising candidate for transcription targeted cancer gene therapy.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
authors.forename: Kirill
authors.initials: K
authors.lastname: Kashkin
authors.forename: Igor
authors.initials: I
authors.lastname: Chernov
authors.forename: Elena
authors.initials: E
authors.lastname: Stukacheva
authors.forename: Galina
authors.initials: G
authors.lastname: Monastyrskaya
authors.forename: Natalya
authors.initials: N
authors.lastname: Uspenskaya
authors.forename: Eugene
authors.initials: E
authors.lastname: Kopantzev
authors.forename: Eugene
authors.initials: E
authors.lastname: Sverdlov
mesh_terms: D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D004258:DNA Polymerase III / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D064111:Minichromosome Maintenance Complex Component 2 / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000097869:Polo-Like Kinase 1
chemical_list: D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D004258:DNA Polymerase III; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C103706:CDC6 protein, human; C093090:CKS1B protein, human; C434055:POLD1 protein, human; C084859:MCM2 protein, human
keywords: CANCER GENE THERAPY; CANCER SPECIFIC; CELL PROLIFERATION; PROMOTER