Enhancer element potentially involved in human survivin gene promoter regulation in lung cancer cell lines

Mityaev, M. V.; Kopantzev, E. P.; Buzdin, Anton; Виноградова, Т. В.

doi:10.1134/s0006297910020082

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…1B ). The activity exhibited by the BIRC5 gene promoter, similar to that in the previous study [12], was higher in all the tumor cell lines as compared to that in normal fibroblasts. The activity of five cloned promoters in the tumor cells was also higher than that in normal fibroblasts ( p < 0.01, Mann–Whitney U test).…”

Section: Resultssupporting

confidence: 88%

“…Parallel transfection of cells with the vectors pGL3 Basic Vector, pGL3 Promoter Vector (Promega, WI), and pGL3- CMV Pr/Enh containing the AseI/BglII fragment of the promoter of early cytomegalovirus genes from the plasmid pEGFP-N1 (Clontech Laboratories, Inc.) in front of the Luc gene was used to standardize the experimental results. In order to compare the tumor specificity of the promoters, the cells were transfected with the 1500-bplong pGL3-based plasmid containing the promoter of the surviving gene ( BIRC5) [12]. The cells were transfected by means of Lipofectamine 2000 (Invitrogen, USA) in 24-well plates according to the manufacturer’s recommendations.…”

Section: Methodsmentioning

confidence: 99%

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Cancer Specificity of Promoters of the Genes Involved in Cell Proliferation Control

et al. 2013

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Core promoters with adjacent regions of the human genes CDC6, POLD1, CKS1B, MCM2, and PLK1 were cloned into a pGL3 vector in front of the Photinus pyrails gene Luc in order to study the tumor specificity of the promoters. The cloned promoters were compared in their ability to direct luciferase expression in different human cancer cells and in normal fibroblasts. The cancer-specific promoter BIRC5 and non-specific CMV immediately early gene promoter were used for comparison. All cloned promoters were shown to be substantially more active in cancer cells than in fibroblasts, while the PLK1 promoter was the most cancer-specific and promising one. The specificity of the promoters to cancer cells descended in the series PLK1, CKS1B, POLD1, MCM2, and CDC6. The bidirectional activity of the cloned CKS1B promoter was demonstrated. It apparently directs the expression of the SHC1 gene, which is located in a “head-to-head” position to the CKS1B gene in the human genome. This feature should be taken into account in future use of the CKS1B promoter. The cloned promoters may be used in artificial genetic constructions for cancer gene therapy.

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Section: Resultssupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Cancer Specificity of Promoters of the Genes Involved in Cell Proliferation Control

et al. 2013

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“…The pair of conditions to be compared in signaling pathway cloud analysis is flexible. In the past, we have compared tumor biopsies to healthy tissue, revealing signaling pathway biomarkers that outperform those of single genes (Kuzmin et al, 2010 ; Mityaev et al, 2010 ; Zabolotneva et al, 2012a , b ), and tissue from old vs. young patients, illustrating how this method may be useful for the screening of potential geroprotectors (Zhavoronkov and Cantor, 2011 ). Other applications include drug discovery and drug repurposing, as well as applications in manipulating cell differentiation.…”

Section: Signaling Pathway Activation Profiles As Drug Targets For Prmentioning

confidence: 99%

Screening and personalizing nootropic drugs and cognitive modulator regimens in silico

Jellen

Aliper

Buzdin³

et al. 2015

Front. Syst. Neurosci.

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The go-to cognitive enhancers of today are those that are widely available rather than optimal for the user, including drugs typically prescribed for treatment of ADHD (e.g., methylphenidate) and sleep disturbances such as narcolepsy (modafinil). While highly effective in their intended therapeutic role, performance gains in healthy populations are modest at best and profoundly inconsistent across subgroups and individuals. We propose a method for in silico screening of possible novel cognitive enhancers followed by high-throughput in vivo and in vitro validation. The proposed method uses gene expression data to evaluate the the collection of activated or suppressed signaling pathways in tissues or neurons of the cognitively enhanced brain. An algorithm maps expression data onto signaling pathways and quantifies their individual activation strength. The collective pathways and their activation form what we term the signaling pathway cloud, a biological fingerprint of cognitive enhancement (or any other condition of interest). Drugs can then be screened and ranked based on their ability to minimize, mimic, or exaggerate pathway activation or suppression within that cloud. Using this approach, one may predict the efficacy of many drugs that may enhance various aspects of cognition before costly preclinical studies and clinical trials are undertaken.

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“…1A). This modified promoter, referred to as P hSurvD , exhibited enhanced transcriptional activity in the majority of p53-negative lung cancer cell lines (21). It must be noted that shortening of the human BIRC5 promoter fragment beyond 1.4 kb upstream of the transcription start site resulted in decreased promoter activity (15).…”

Section: Introductionmentioning

confidence: 99%

hTERT and BIRC5 gene promoters for cancer gene therapy: A comparative study

et al. 2016

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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 of hTERT, human BIRC5 and mouse Birc5 promoters and their modifications were compared in 10 human cancer cell lines using the luciferase reporter gene activity assay. The results revealed that BIRC5-and hTERT-based promoters had strikingly different cell specificities with comparable activities in only 40% of cell lines. Importantly, relative hTERT and BIRC5 transcript abundance cannot be used to predict the most potent promoter. Among the hTERT-based promoters that were assessed, modification with the minimal cytomegalovirus promoter generally resulted in the most potent activity. Mouse Birc5 and modified human BIRC5 promoters 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. IntroductionTranscriptional targeting in gene therapy is an approach based on the use of tissue-specific or tumor-specific promoters (TSPs) to direct the expression of therapeutic genes specifically to a tumor (1). It is assumed that it must meet the requirements of transgene expression in tumor tissues but not in normal tissues. This combination of 'tumor on' and 'normal tissue off' profile can result in an increase in the therapeutic index and limit the toxicity of vectors and transgenes in vivo. Numerous promoters have already been evaluated for transcriptional targeting in cancer gene therapy [for reviews, see (2-4)], such as the α-fetoprotein promoter for hepatic carcinoma, tyrosinase gene promoter for melanoma, prostate-specific antigen promoter for prostate cancer, cyclooxygenase-2 promoter for gastrointestinal cancer, midkine promoter for Wilms' tumor or neuroblastoma, chemokine (C-X-C motif) receptor 4 promoter for breast cancer and melanoma, hypoxia-inducible promoter for hypoxic tumor-targeting gene therapy, promoter of the carcinoembryonic antigen gene (5), and numerous others. However, many of the gene promoters used for this goal have been shown to be abundantly expressed in a variety of normal tissues (4), such that their usage also affects normal host cells, thus increasing the risk of unwanted side effects. TSPs that are expressed in a wide variety of tumors and have low expression in normal tissue are highly desirable to meet gene therapy demands. Two gene promoters frequently used for the gene therapeutic purposes appear to most completely satisfy the requirements: The human telomerase reverse transcriptase (hTERT) promoter, and the promoter driving the expression of BIRC5, encoding the apoptosis inhibitor survivin.Survivin is one of the central players of c...

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Enhancer element potentially involved in human survivin gene promoter regulation in lung cancer cell lines

Cited by 9 publications

References 38 publications

Cancer Specificity of Promoters of the Genes Involved in Cell Proliferation Control

Cancer Specificity of Promoters of the Genes Involved in Cell Proliferation Control

Screening and personalizing nootropic drugs and cognitive modulator regimens in silico

hTERT and BIRC5 gene promoters for cancer gene therapy: A comparative study

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