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Transcriptional Upregulation (transcriptional + upregulation)
Selected AbstractsTranscriptional upregulation of inflammatory cytokines in human intestinal epithelial cells following Vibrio cholerae infectionFEBS JOURNAL, Issue 17 2007Arunava Bandyopadhaya Coordinated expression and upregulation of interleukin-1,, interleukin-1,, tumor necrosis factor-,, interleukin-6, granulocyte,macrophage colony-stimulating factor, interleukin-8, monocyte chemotactic protein-1 (MCP-1) and epithelial cell derived neutrophil activator-78, with chemoattractant and proinflammatory properties of various cytokine families, were obtained in the intestinal epithelial cell line Int407 upon Vibrio cholerae infection. These proinflammatory cytokines also showed increased expression in T84 cells, except for interleukin-6, whereas a striking dissimilarity in cytokine expression was observed in Caco-2 cells. Gene expression studies of MCP-1, granulocyte,macrophage colony-stimulating factor, interleukin-1,, interleukin-6 and the anti-inflammatory cytokine transforming growth factor-, in Int407 cells with V. cholerae culture supernatant, cholera toxin, lipopolysaccharide and ctxA mutant demonstrated that, apart from cholera toxin and lipopolysaccharide, V. cholerae culture supernatant harbors strong inducer(s) of interleukin-6 and MCP-1 and moderate inducer(s) of interleukin-1, and granulocyte,macrophage colony-stimulating factor. Cholera toxin- or lipopolysaccharide-induced cytokine expression is facilitated by activation of nuclear factor-,B (p65 and p50) and cAMP response element-binding protein in Int407 cells. Studies with ctxA mutants of V. cholerae revealed that the mutant activates the p65 subunit of nuclear factor-,B and cAMP response element-binding protein, and as such the activation is mediated by cholera toxin-independent factors as well. We conclude that V. cholerae elicits a proinflammatory response in Int407 cells that is mediated by activation of nuclear factor-,B and cAMP response element-binding protein by cholera toxin, lipopolysaccharide and/or other secreted products of V. cholerae. [source] Transcriptional upregulation of HSP70-2 by HIF-1 in cancer cells in response to hypoxiaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Wen-Jie Huang Abstract Heat shock protein 70-2 (HSP70-2) can be expressed by cancer cells and act as an important regulator of cancer cell growth and survival. Here, we show the molecular mechanisms by which hypoxia regulate HSP70-2 expression in cancer cells. When cells were subjected to hypoxia (1% O2), the expression of HSP70-2 had a significant increase in cancer cells. Such increase was due to the direct binding of hypoxia-inducible factor to hypoxia-responsive elements (HREs) in the HSP70-2 promoter. By luciferase assays, we demonstrated that the HRE1 at position ,446 was essential for transcriptional activation of HSP70-2 promoter under hypoxic conditions. We also demonstrated that HIF-1, binds to the HSP70-2 promoter and the binding is specific, as revealed by HIF binding/competition and chromatin immunoprecipitation assays. Consequently, the upregulation of HSP70-2 enhanced the resistance of tumor cells to hypoxia-induced apoptosis. These findings provide a new insight into how tumor cells overcome hypoxic stress and survive, and also disclose a new regulatory mechanism of HSP70-2 expression in tumor cells. © 2008 Wiley-Liss, Inc. [source] Transcriptional upregulation and unmethylation of the promoter region of p16 in invasive basal cell carcinoma cells and partial co-localization with the ,2 chain of laminin-332,THE JOURNAL OF PATHOLOGY, Issue 1 2007S Svensson Månsson Abstract Basal cell carcinoma cells show low proliferation rates at the invasive front and a concordant upregulation of the cdk-inhibitor p16, limiting proliferative capacity. Little is known about the mechanisms of p16 regulation in normal and malignant cells apart from that many transcription factors such as Ets1, Ets2, SP1, SP3, JunB and the polycomb protein Bmi1 have the potential to induce or repress p16 expression. Therefore, the aim of this study was to determine how p16 is regulated in basal cell carcinoma with special focus on its upregulation in invasive cells. By analysing various microdissected areas of basal cell carcinoma using real-time quantitative PCR we observed upregulation of p16 mRNA in invasive tumour cells compared to centrally localized tumour cells. The methylation status of the p16 promoter, analysed by methylation-specific PCR, also showed diminished methylation in tumour cells at the invasive front, supporting the hypothesis that promoter methylation can affect the transcriptional activation of p16 in vivo. There was only sporadic co-localization of Ets, or ERK1/2 phosphorylation with p16 upregulation at the invasive front, suggesting that these factors were not directly involved in the regulation of p16. Furthermore, the ,2 chain of laminin-332 has been reported to be increased at the invasive front compared to the central areas of many tumours. Interestingly, in basal cell carcinoma we observed partial co-localization between p16 and the ,2 chain of laminin-332 in tumour cells towards areas of ulceration and in the majority of clearly infiltrative tumour cells but not in p16 positive tumour cells with a more pushing invasive growth pattern. These data suggest that concurrent p16 upregulation and decreased proliferation are more general phenomena in different types of invasive growth patterns in basal cell carcinomas and that these only partially overlap with the ,2 chain of laminin-332 associated invasion patterns. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Frequency and characterization of HMGA2 and HMGA1 rearrangements in mesenchymal tumors of the lower genital tractGENES, CHROMOSOMES AND CANCER, Issue 11 2007Fabiola Medeiros Mesenchymal tumors of the lower genital tract predominantly occur in women of reproductive age and are mainly represented by aggressive angiomyxoma (AAM) and angiomyofibroblastoma (AMF). Whether these tumors are different phenotypic expressions of the same biological entity is still debatable. Genetic rearrangements of HMGA2 have been reported in a few cases of AAM but its frequency and clinicobiological implications have not been studied systematically. We evaluated 90 cases of mesenchymal tumors of the lower genital tract that comprised 42 AAMs, 18 AMFs, 6 cellular angiofibromas, 5 fibroepithelial stromal polyps, 15 genital leiomyomas, 3 superficial angiomyxomas, and 1 spindle cell lipoma. Fluorescence in situ hybridization was used to identify rearrangements of HMGA2 and its homologue HMGA1. HMGA2 rearrangements were identified in 14 AAMs (33%) and in 1 vaginal leiomyoma. All other tumors were negative for HMGA2 rearrangements. HMGA1 rearrangement was not found in any of the cases. RT-PCR confirmed transcriptional upregulation of HMGA2 only in tumors with HMGA2 rearrangements. Standard cytogenetic analyses were performed in two AAMs and one AMF. One AAM had a t(1;12)(p32;q15); the other tumors had normal karyotypes. Mapping and sequence analysis of the breakpoint showed fusion to the 3, untranslated region of HMGA2 to genomic sequences derived from the contig NT 032977.8 on chromosome 1p32. Our findings support the hypothesis that AAM and AMF are distinct biological entities. The diagnostic usefulness of HMGA2 rearrangements to differentiate between AAM and other tumors of the lower genital tract may be limited due to the their low frequency. © 2007 Wiley-Liss, Inc. [source] GAB2 is a novel target of 11q amplification in AML/MDSGENES, CHROMOSOMES AND CANCER, Issue 9 2006Andrea Zatkova Chromosome arm 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are rare but recurrent aberrations in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We have recently shown that in addition to the MLL core amplicon, independent sequences in 11q23,24 and/or 11q13.5 are coamplified within the same cytogenetic markers in 90% and 60% of patients, respectively. Here we further narrow down the minimal amplicon in 11q13.5 to 1.17 Mb by means of semi-quantitative PCR and FISH analyses. The newly defined amplicon contains seven genes, including the GRB2 -associated binding protein 2 (GAB2). Using real-time RT-PCR we show a significant transcriptional upregulation of GAB2 in the patients who have GAB2 coamplified with MLL. Thus, the adaptor molecule GAB2 that has already been shown to enhance oncogenic signaling in other neoplasias appears as a novel target of 11q amplification in AML/MDS. © 2006 Wiley-Liss, Inc. [source] X-chromosome upregulation and inactivation: two sides of the dosage compensation mechanism in mammalsBIOESSAYS, Issue 1 2009Elena V. Dementyeva Abstract Mammals have a very complex, tightly controlled, and developmentally regulated process of dosage compensation. One form of the process equalizes expression of the X-linked genes, present as a single copy in males (XY) and as two copies in females (XX), by inactivation of one of the two X-chromosomes in females. The second form of the process leads to balanced expression between the X-linked and autosomal genes by transcriptional upregulation of the active X in males and females. However, not all X-linked genes are absolutely balanced. This review is focused on the recent advances in studying the dosage compensation phenomenon in mammals. [source] | ||||||||||