Comparison of miRNA expression in Dickkopf1-expressing versus control newborn mouse skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Arabidopsis thaliana Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE4723 | GEO | 2006/05/04
SECONDARY ACCESSION(S): PRJNA95699
REPOSITORIES: GEO
Similar Datasets
Project description:miRNA expression was compared in skin from control newborn mice and littermate mice ectopically expressing the potent secreted WNT inhibitor Dickkopf 1 (DKK1) in the epidermis. DKK1 completely suppresses hair follicle development. Multiple miRNAs were identified that reproducibly produced signals above background in both types of skin sample. Several miRNAs were identified for which hybridization signals were on average more than 2.5 fold higher in control samples than in Dkk1-expressing samples, suggesting these may be upregulated in hair follicles, and/or are direct or indirect targets of WNT inhibition in the skin. Keywords: miRNA expression array, transgenic mouse, skin, WNT Low molecular weight RNA was isolated using the mirVana RNA extraction kit (Ambion) from full thickness dorsal skin of three K5-rtTA; tetO-Dkk1 newborn mice and three control littermates following doxycycline treatment from E0.5 to induce expression of Dkk1 in double transgenic epidermis [1]. Control and Dkk1âexpressing transgenic samples were tagged for labeling with Cy3 and Cy5 dyes respectively using the Ncode miRNA Labeling System (Invitrogen), mixed by equal mass, and co-hybridized to miRNA arrays that have been described previously [2]. Background-corrected median signals for pixels from each probe spot in both the Cy3 and Cy5 channels were used for analysis. Cy3 (control samples C2, C4, C5) was detected at 532nm and Cy5 (Dkk1âexpressing transgenic samples TG1, TG2, TG4) at 635 nm. References: [1] Chu, E.Y., Hens, J., Andl, T., Kairo, A., Yamaguchi, T.P., Brisken, C., Glick, A., Wysolmerski, J.J., and Millar, S.E. (2004). Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131, 4819-4829. [2] Nelson, P.T., Baldwin, D.A., Scearce, L.M., Oberholtzer, J.C., Tobias, J.W., and Mourelatos, Z. (2004). Microarray-based, high-throughput gene expression profiling of microRNAs. Nat Methods 1, 155-161.
2010-06-11 | E-GEOD-4723 | biostudies-arrayexpress
Project description:Dickkopf 1 (DKK1), which is expressed at high mRNA levels by fibroblasts in the dermis of human skin on the palms and soles, inhibits the function and proliferation of melanocytes in the epidermis of those areas via the suppression of beta-catenin and microphthalmia-associated transcriptor factor (MITF). In this study, we investigated the effects of DKK1 on melanocyte gene expression profiles and on Wnt signaling pathways using DNA microarray technology. Keywords: compound treatment design
2006-11-30 | GSE5515 | GEO
Project description:Canonical Wnt signaling controls proliferation and differentiation of osteogenic progenitor cells, and tumor-derived secretion of the Wnt antagonist Dickkopf-1 (Dkk1) is correlated with osteolyses and metastasis in many bone malignancies. However, the role of Dkk1 in the oncogenesis of primary osteosarcoma (OS) remains unexplored. Here, we over-expressed Dkk1 in the OS cell line MOS-J. Contrary to expectations, Dkk1 had autocrine effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro. In vivo, Dkk1 expressing MOS-J cells formed larger and more destructive tumors than controls. These effects were attributed in part to up-regulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) through Jun-N-terminal kinase signaling. This is the first report linking Dkk1 to tumor stress resistance, further supporting the targeting of Dkk1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells. Two samples were analyzed, one human DKK1 transfected MOS-J cell sample and one control vector transfected MOS-J cell sample.
2012-12-22 | E-GEOD-43112 | biostudies-arrayexpress
Project description:Canonical Wnt signaling controls proliferation and differentiation of osteogenic progenitor cells, and tumor-derived secretion of the Wnt antagonist Dickkopf-1 (Dkk1) is correlated with osteolyses and metastasis in many bone malignancies. However, the role of Dkk1 in the oncogenesis of primary osteosarcoma (OS) remains unexplored. Here, we over-expressed Dkk1 in the OS cell line MOS-J. Contrary to expectations, Dkk1 had autocrine effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro. In vivo, Dkk1 expressing MOS-J cells formed larger and more destructive tumors than controls. These effects were attributed in part to up-regulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) through Jun-N-terminal kinase signaling. This is the first report linking Dkk1 to tumor stress resistance, further supporting the targeting of Dkk1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells.
2012-12-22 | GSE43112 | GEO
Project description:Neuroblastomas are tumors of the developing peripheral sympathetic nervous system, which originates from the neural crest. Twenty percent of neuroblastomas show amplification of the MYCN oncogene, which correlates with poor prognosis. The MYCN transcription factor can activate and repress gene expression. To broaden our insight in the spectrum of genes down-regulated by MYCN, we generated gene expression profiles of the neuroblastoma cell lines SHEP-21N and SKNAS-NmycER, in which MYCN activity can be regulated. In this study, we show that MYCN suppresses the expression of Dickkopf-1 (DKK1) in both cell lines. DKK1 is a potent inhibitor of the wnt/beta-catenin signalling cascade, which is known to function in neural crest cell migration. We generated a DKK1 inducible cell line, IMR32-DKK1, which showed impaired proliferation upon DKK1 expression. Surprisingly, DKK1 expression did not inhibit the canonical wnt/beta-catenin signalling, suggesting a role of DKK1 in an alternative route of the wnt pathway. Gene expression profiling of two IMR32-DKK1 clones showed that only a few genes, amongst which SYNPO2, were up-regulated by DKK1. SYNPO2 encodes an actin-binding protein and was previously found to inhibit proliferation and invasiveness of prostate cancer cells. These results suggest that MYCN might stimulate cell proliferation by inhibiting the expression of DKK1. DKK1 might exert part of its growth suppressive effect by induction of SYNPO2 expression. Keywords: DKK1, MYCN, neuroblastoma, Dickkopf
2007-08-24 | GSE8066 | GEO
Project description:Dickkopf 1 (DKK1), which is expressed at high mRNA levels by fibroblasts in the dermis of human skin on the palms and soles, inhibits the function and proliferation of melanocytes in the epidermis of those areas via the suppression of beta-catenin and microphthalmia-associated transcriptor factor (MITF). In this study, we report that treatment of keratinocytes with DKK1 increases their proliferation and decreases their uptake of melanin, and that treatment of reconstructed skin with DKK1 induces a thicker and less pigmented epidermis. We investigated the effects of DKK1 on keratinocytes using DNA microarray technology. Keywords: compound treatment design
2007-12-31 | GSE9211 | GEO
Project description:Dickkopf 1 (DKK1), which is expressed at high mRNA levels by fibroblasts in the dermis of human skin on the palms and soles, inhibits the function and proliferation of melanocytes in the epidermis of those areas via the suppression of beta-catenin and microphthalmia-associated transcriptor factor (MITF). In this study, we investigated the effects of DKK1 on melanocyte gene expression profiles and on Wnt signaling pathways using DNA microarray technology. Paired cDNA samples, labeled by cyanine 3- and cyanine 5-dUTP incorporation (Qiagen, Valencia, CA) during reverse transcription (Qiagen), were hybridized simultaneously with one oligo-DNA chip (HS-Operon V2vB2.2p13) as per NCI in-house protocol (available at http://mach1.nci.nih.gov/). Two fluorescent intensities of the oligo-DNA chip were scanned using a microarray scanner (GenePix 4000A, Axon Instruments, Inc., Molecular Device Corp., Sunnyvale, CA).
2010-06-30 | E-GEOD-5515 | biostudies-arrayexpress
Project description:Neuroblastomas are tumors of the developing peripheral sympathetic nervous system, which originates from the neural crest. Twenty percent of neuroblastomas show amplification of the MYCN oncogene, which correlates with poor prognosis. The MYCN transcription factor can activate and repress gene expression. To broaden our insight in the spectrum of genes down-regulated by MYCN, we generated gene expression profiles of the neuroblastoma cell lines SHEP-21N and SKNAS-NmycER, in which MYCN activity can be regulated. In this study, we show that MYCN suppresses the expression of Dickkopf-1 (DKK1) in both cell lines. DKK1 is a potent inhibitor of the wnt/ï?¢-catenin signalling cascade, which is known to function in neural crest cell migration. We generated a DKK1 inducible cell line, IMR32-DKK1, which showed impaired proliferation upon DKK1 expression. Surprisingly, DKK1 expression did not inhibit the canonical wnt/ï?¢-catenin signalling, suggesting a role of DKK1 in an alternative route of the wnt pathway. Gene expression profiling of two IMR32-DKK1 clones showed that only a few genes, amongst which SYNPO2, were up-regulated by DKK1. SYNPO2 encodes an actin-binding protein and was previously found to inhibit proliferation and invasiveness of prostate cancer cells. These results suggest that MYCN might stimulate cell proliferation by inhibiting the expression of DKK1. DKK1 might exert part of its growth suppressive effect by induction of SYNPO2 expression. Experiment Overall Design: Single time course experiment, including 4 time points
2008-06-16 | E-GEOD-8066 | biostudies-arrayexpress
Project description:Inflammatory arthritis is associated with bone loss and fractures due to abnormal bone remodelling. Bone remodelling is 'uncoupled' with bone resorption increased and bone formation suppressed. These changes resemble those seen in patients treated with therapeutic glucocorticoids, and in both of these situations, altered wnt signalling is implicated. Recent studies have highlighted the importance of the synovial fibroblast in mediating abnormal bone remodelling during inflammation. The wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation, and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Here we show that DKK1 expression by primary human synovial fibroblasts is more potently regulated by glucocorticoids than pro-inflammatory cytokines. Glucocorticoids, but not TNF-alpha, regulated expression of multiple wnt agonists and antagonists in favour of inhibition of wnt signalling. In vitro TNF-alpha and IL1-beta indirectly regulate DKK1 production through increased expression of the glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). These results demonstrate that the links between synovial inflammation, altered wnt signalling and bone remodelling may not be direct but are dependent on local activation of endogenous glucocorticoids.
2012-04-24 | GSE37520 | GEO
Project description:Inflammatory arthritis is associated with bone loss and fractures due to abnormal bone remodelling. Bone remodelling is 'uncoupled' with bone resorption increased and bone formation suppressed. These changes resemble those seen in patients treated with therapeutic glucocorticoids, and in both of these situations, altered wnt signalling is implicated. Recent studies have highlighted the importance of the synovial fibroblast in mediating abnormal bone remodelling during inflammation. The wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation, and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Here we show that DKK1 expression by primary human synovial fibroblasts is more potently regulated by glucocorticoids than pro-inflammatory cytokines. Glucocorticoids, but not TNF-alpha, regulated expression of multiple wnt agonists and antagonists in favour of inhibition of wnt signalling. In vitro TNF-alpha and IL1-beta indirectly regulate DKK1 production through increased expression of the glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). These results demonstrate that the links between synovial inflammation, altered wnt signalling and bone remodelling may not be direct but are dependent on local activation of endogenous glucocorticoids. Human fibroblast-like synoviocytes isolated from patients with rheumatoid arthritis treated with either vehicle, TNF or dexamethasone (dex). Gene arrays for control, TNF and dexamethasone treatments were performed on three separate synovial fibroblast cell lines isolated from three rheumatoid arthritis patients. All fold changes displayed are the combined results of the three separate fibroblast lines.
2012-04-24 | E-GEOD-37520 | biostudies-arrayexpress