A genomic-scale view of the cAMP response element-enhancer decoy: A tumor target-based genetic tool

Cho, Yee Sook; Kim, Meyoung Kon; Cheadle, Chris; Neary, Catherine; Park, Yun Gyu; Becker, Kevin G.; Cho‐Chung, Yoon S.

doi:10.1073/pnas.242617799

Cited by 26 publications

(30 citation statements)

References 32 publications

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“…Because the CRE cis-element, TGACGTCA, is palindromic, a synthetic single-stranded oligonucleotide composed of the CRE sequence self-hybridizes to form a duplex/hairpin. This oligonucleotide inhibits CRE-and AP-1-directed gene transcription and promotes growth inhibition in vitro and in vivo in a broad spectrum of cancer cells, without adversely affecting normal cell growth (25,56). CRE- decoy oligonucleotides may provide a powerful new means of combating cancers, and other pathological conditions by regulating the expression of cAMP-responsive genes (25).…”

Section: Discussionmentioning

confidence: 99%

Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells

Han

Ritzenthaler

Sitaraman

et al. 2006

Journal of Biological Chemistry

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Matrix metalloproteinases (MMPs) 2 are a family of zinc enzymes responsible for degradation of extracellular matrix components including basement membrane collagen, interstitial collagens, fibronectin (FN), and various proteoglycans during normal remodeling and repair processes (1, 2). The potent proteolytic activities of MMPs are mainly regulated by the concomitant expression of specific tissue inhibitors of matrix metalloproteinases (3). Excessive or inappropriate expression of MMPs may contribute to the pathogenesis of tissue destructive processes in a wide variety of diseases including lung disorders like bronchial asthma, chronic obstructive pulmonary disease, acute lung injury, pulmonary hypertension, and interstitial lung diseases (2, 4). In addition, MMPs have been implicated in the progression and metastases of different tumors including lung cancer (see later in text).One member of the MMP family is the 92-kDa type IV collagenase MMP-9. The MMP-9 gene is encoded on chromosome 20 and its expression is under the control of a 2.2-kb upstream regulatory sequence harboring binding sites for AP-1, NF-B, Sp1, and others (5). MMP-9 expression is increased in malignant cancers when compared with benign tumors and non-invasive ones, and there is compelling in vitro and in vivo evidence for a role of MMP-9 in tumor invasion and angiogenesis (6, 7). Its dramatic overexpression in cancer and various inflammatory conditions suggest that this protease is a potential target for the development of novel therapeutic interventions (8).Because of its perceived importance, our research focuses on the factors that increase MMP-9 expression in the lung. Our search led us to FN, a matrix glycoprotein highly expressed in tobacco-related lung disease that has been shown to stimulate lung carcinoma cell growth through several mechanisms (9 -11). Cell adhesion to FN results in MMP secretion in normal and tumor cell systems (12)(13)(14). These studies suggest that tumor cell interactions with FN might lead to MMP-9 expression thereby promoting cancer cell migration, invasion, and related processes. However, the mechanisms by which FN stim-* This work was supported by American Lung Association Bioresearch Grant RG-10215N (to S. W. H.) and by a Merit Review Grant from the Department of Veterans Affairs (to J. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.

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Section: Discussionmentioning

confidence: 99%

Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells

Han

Ritzenthaler

Sitaraman

et al. 2006

Journal of Biological Chemistry

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“…It has been demonstrated that CRE-decoy oligonucleotides inhibit activator proteins 1 and 2 CRE-directed gene transcription in vivo and in vitro, altering the expression of a variety of cluster genes associated with tumor progression (29,45). Unlike the experimental setup using the CRE-decoy, which affects all of the F, analysis of the effects of the different CREB mutations on tumor progression was monitored noninvasively using magnetic resonance imaging.…”

Section: Discussionmentioning

confidence: 99%

“…Several cell cycle genes such as cyclinD1 and cyclin A are regulated by CREB via a functional CRE element (25)(26)(27). Microarray analysis of PC3M cells treated with CRE decoy oligodeoxynucleotide (ODN) revealed that many genes related to tumor growth are regulated by the CREB family of transcription factors (28,29).…”

Section: Introductionmentioning

confidence: 99%

A Pivotal Role of Cyclic AMP-Responsive Element Binding Protein in Tumor Progression

Abramovitch¹,

et al. 2004

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Tumor microenvironment controls the selection of malignant cells capable of surviving in stressful and hypoxic conditions. The transcription factor, cyclic AMP-responsive element binding (CREB) protein, activated by multiple extracellular signals, modulates cellular response by regulating the expression of a multitude of genes. Previously, we have demonstrated that two cystein residues, at the DNA binding domain of CREB, mediate activation of CREB-dependent gene expression at normoxia and hypoxia. The construction of a dominant-positive CREB mutant, insensitive to hypoxia cue (substitution of two cystein residues at position 300 and 310 with serine in the DNA binding domain) and of a dominant negative CREB mutant (addition of a mutation in serine 133 ), enabled a direct assessment, in vitro and in vivo, of the role of CREB in tumor progression. In this work, we demonstrate both in vitro and in vivo that CREB controls hepatocellular carcinoma growth, supports angiogenesis, and renders resistance to apoptosis. Along with the identification, by DNA microarray, of the CREB-regulated genes in normoxia and hypoxia, this work demonstrates for the first time that in parallel to other hypoxia responsive mechanisms, CREB plays an important role in hepatocellular carcinoma tumor progression.

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“…Decoys presumably bind and sequester the targeted transcription factor, rendering it unavailable for transcription of downstream target genes, thus resulting in specific transcriptional inhibition. A transcription factor decoy approach was originally used for the study of gene expression mediated by transcription factors (Gambarotta et al, 1996;Cho et al, 2002). Because of the sequence-specific characteristics of a transcription factor decoy, it is an attractive approach to target transcription factors.…”

Section: Stat3 Decoy Effect On Stat1 Signaling In Scchn 1441mentioning

confidence: 99%

Antiproliferative Mechanisms of a Transcription Factor Decoy Targeting Signal Transducer and Activator of Transcription (STAT) 3: The Role of STAT1

et al. 2007

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We previously developed a transcription factor decoy targeting signal transducer and activator of transcription 3 (STAT3) and reported antitumor activity in both in vitro and in vivo models of squamous cell carcinoma of the head and neck (SCCHN). Based on the known existence of STAT1-STAT3 heterodimers, the high sequence homology between STAT1 and STAT3, as well as expression of both STAT1 and STAT3 in SCCHN, we examined whether the STAT3 decoy interferes with STAT1 signaling. SCCHN cell lines with different STAT1 expression levels (but similar STAT3 levels) were used. Both cell lines were sensitive to the growth-inhibitory effects of the STAT3 decoy compared with a mutant control decoy. Intact STAT1 signaling was demonstrated by interferon-␥ (IFN-␥)-mediated induction of STAT1 phosphorylation (Tyr701) and interferon-regulatory factor-1 (IRF-1) expression. Treatment with the STAT3 decoy (but not a mutant control decoy) resulted in inhibition of IRF-1 protein expression in both cell lines, indicating specific inhibition of STAT1 signaling by the STAT3 decoy. Because STAT1 is a potential tumor suppressor, we also investigated whether STAT1 signaling mitigated the therapeutic efficacy of the STAT3 decoy. In both PCI-15B and UM-22B cells, STAT1 siRNA treatment resulted in decreased STAT1 expression, without altering the antitumor activity of the STAT3 decoy. Likewise, the antitumor effects of the STAT3 decoy were not altered by STAT1 activation upon IFN-␥ treatment. These results suggest that the therapeutic mechanisms of STAT3 blockade using a transcription factor decoy are independent of STAT1 activation.Signal transducer and activator of transcription 3 (STAT3) has emerged as a potential molecular target for cancer therapy. STAT3 is constitutively activated and overexpressed in a variety of human malignancies, including breast, lung, prostate, brain, leukemia, multiple myeloma, and squamous cell carcinoma of the head and neck (SCCHN) (Grandis et al., 1998;Turkson and Jove, 2000). The expression levels of activated or tyrosine-phosphorylated STAT3 have been reported to correlate with decreased survival in several cancers, including oral tongue carcinoma (Masuda et al., 2002). Molecular targeting of STAT3 using a variety of strategies in preclinical models of human cancer has been shown to inhibit tumor growth (Turkson and Jove, 2000). We previously developed a transcription factor decoy based on the STAT3 DNA binding element and demonstrated that this decoy interferes with STAT3 signaling and decreases SCCHN tumor growth in vitro and in vivo (Leong et al., 2003;Xi et al., 2005).Transcription factor decoys are double-stranded DNA oligonucleotides that resemble the transcription factor-binding site in the promoters of target genes. Transcription factor decoys presumably bind transcription factors and sequester the targeted transcription factor, rendering it unavailable for transcription of downstream target genes. The sequence of the STAT3 decoy was derived from the serum-inducible element of the human c-fos...

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A genomic-scale view of the cAMP response element-enhancer decoy: A tumor target-based genetic tool

Cited by 26 publications

References 32 publications

Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells

Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells

A Pivotal Role of Cyclic AMP-Responsive Element Binding Protein in Tumor Progression

Antiproliferative Mechanisms of a Transcription Factor Decoy Targeting Signal Transducer and Activator of Transcription (STAT) 3: The Role of STAT1

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