Eukaryotic expression vectors and immunoconjugates for cancer therapy

Glinka, E. M.; Edelweiss, Evelina; Deyev, Sergey M.

doi:10.1134/s0006297906060022

Cited by 4 publications

(2 citation statements)

References 116 publications

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“…Although identification of a selective sweep provides considerable evidence for positive selection (Glinka et al, 2003; Orengo and Aguade, 2004; DuMont and Aquadro, 2005; Ometto et al, 2005; Glinka et al, 2006; Pool et al, 2006; Hutter et al, 2007; Orengo and Aguade, 2007; Beisswanger and Stephan, 2008), they are not entirely conclusive of adaptive evolution for several reasons. First, there is uncertainty about the correct demographic model for D. melanogaster .…”

Section: The First Genome-wide Scan For Recent Te-induced Adaptationsmentioning

confidence: 99%

The adaptive role of transposable elements in the Drosophila genome

González¹,

Petrov²

2009

Gene

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Transposable elements (TEs) are short DNA sequences with the capacity to move between different sites in the genome. This ability provides them with the capacity to mutate the genome in many different ways, from subtle regulatory mutations to gross genomic rearrangements. The potential adaptive significance of TEs was recognized by those involved in their initial discovery although it was hotly debated afterwards. For more than two decades, TEs were considered to be intragenomic parasites leading to almost exclusively detrimental effects to the host genome. The sequencing of the Drosophila melanogaster genome provided an unprecedented opportunity to study TEs and led to the identification of the first TE-induced adaptations in this species. These studies were followed by a systematic genome-wide search for adaptive insertions that allowed for the first time to infer that TEs contribute substantially to adaptive evolution. This study also revealed that there are at least twice as many TE-induced adaptations that remain to be identified. To gain better understanding of the adaptive role of TEs in the genome we clearly need to (i) identify as many adaptive TEs as possible in a range of Drosophila species as well as (ii) carry out in-depth investigations of the effects of adaptive TEs on as many phenotypes as possible.Keywords transposable elements; adaptation; Drosophila; in situ; bottlenecks; selfish DNA What is a transposable element?Transposable Elements (TEs) are short DNA sequences, typically 1-10kb, capable of inserting copies of themselves into new genomic locations. TEs are an ancient, abundant and diverse component of eukaryotic genomes. They are present in virtually all eukaryotic species investigated so far where they represent from 3% to 80% of the total DNA (Hua- Van et al., 2005;Biemont and Vieira, 2006;Piegu et al., 2006). Most TEs can be assigned to one of two main classes defined according to their mode of transposition (Figure 1). Class I or retrotransposons use a "copy and paste" mechanism that involves an RNA intermediate. Retrotransposons are further subdivided into those that have long terminal repeats (LTRs) and those that do not (long and short interspersed nuclear elements (LINEs and SINEs)). Class II or DNA transposons utilize a "cut and paste" mechanism that involves a DNA intermediate. Inside these two classes, TEs are further classified into superfamilies according to featuresCorresponding author: Josefa González, Department of Biology, 371 Serra St., Stanford University, Stanford CA 94305-3020, e-mail: jgonzalp@stanford.edu, phone: 650-7362240. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and a...

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Section: The First Genome-wide Scan For Recent Te-induced Adaptationsmentioning

confidence: 99%

The adaptive role of transposable elements in the Drosophila genome

González¹,

Petrov²

2009

Gene

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“…Survivin is one of the central players of cancer development (1,(6)(7)(8), and the BIRC5 gene (9) promoter is also active in wide spectrum of cancer cells (10)(11)(12)(13). In normal tissues, survivin expression is found during embryonic and fetal development but is largely undetectable in terminally differentiated adult tissues (14).…”

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

Mityaev

Kopantzev

Buzdin

et al. 2010

Biochemistry Moscow

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We have revealed evolutionarily conserved regions in a 4500-bp DNA sequence 5'-adjacent to the survivin (BIRC5) gene. In the transcribed region of the BIRC5 gene we have detected and characterized in detail a 3'-fragment of the CpG island that stimulated in enhancer-like way the gene promoter activity in normal cells and in a number of cancer, in particular lung cancer, cell lines. When added to the initial 1498-bp survivin promoter region, a transcribed DNA fragment of a CpG island approximately twofold enhanced the promoter activity in cancer cells and in normal lung fibroblasts. The observed effect did not depend upon the orientation of the fragment and distances between the fragment and the transcription initiation site. In the case of a heterologous SV40 virus promoter, the effect was less pronounced. In addition to earlier reports, the results provide new information on the BIRC5 gene expression regulation and also demonstrate that this gene exon sequences can play a significant role in BIRC5 gene expression regulation. The data provide another possibility to increase survivin promoter activity without changing its cancer specificity for application in cancer (in particular, lung cancer) gene therapy.

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Eukaryotic expression vectors and immunoconjugates for cancer therapy

Cited by 4 publications

References 116 publications

The adaptive role of transposable elements in the Drosophila genome

The adaptive role of transposable elements in the Drosophila genome

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

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

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