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Repression of genes for stimulators of glycolysis

ABSTRACT: The overall aim of the present work was to identify MTG16 functions in leukemia cells. Alterations in quantity of the MTG16 co-repressor might affect gene regulation and cell metabolism in malignant cells. Differentiated cells secure energy for cellular homeostasis largely by mitochondrial oxidation. Whereas, mature cells, proliferating tumour cells including leukemia cells depend on glycolysis and mitochondrial respiration may be low even in oxygen–rich environments.The same signal transduction pathways that govern cell proliferation give instructions for nutrient uptake and co-regulate metabolic processes. In this manner, the metabolism of tumor cells, and other highly proliferating cells, is adapted to stimulate anabolic glycolysis–driven processes for incorporation of nutrients into nucleotides, amino acids and lipids to synthesize macromolecules required for growth and proliferation. We used a doxycycline–regulated Tet-On gene expression system to achieve controlled expression of MTG16. A noticeable finding was that the expression of genes for key glycolytic regulators involved in aerobic tumor cell glycolysis was diminished by MTG16. Total cellular RNA was extracted from Raji/MTG16 Tet-On 3G cells after 8 hours of incubation with 1 mg/ml doxycycline. Cells were collected in triplicates as biological replicates. Total RNA was isolated using the RNeasy mini kit. The quality of RNA was examined by Bioanalyzer.RevertAidTM was used for synthesis of first strand cDNA from 1mg RNA using random primers.Microarray analysis was performed using Affymetrix expression system at SCIBLU Genomics.

ORGANISM(S): Homo sapiens

SUBMITTER: Ram Ajore

PROVIDER: E-GEOD-42682 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Repression of genes for stimulators of glycolysis

Project description:The overall aim of the present work was to identify MTG16 functions in leukemia cells. Alterations in quantity of the MTG16 co-repressor might affect gene regulation and cell metabolism in malignant cells. Differentiated cells secure energy for cellular homeostasis largely by mitochondrial oxidation. Whereas, mature cells, proliferating tumour cells including leukemia cells depend on glycolysis and mitochondrial respiration may be low even in oxygen–rich environments.The same signal transduction pathways that govern cell proliferation give instructions for nutrient uptake and co-regulate metabolic processes. In this manner, the metabolism of tumor cells, and other highly proliferating cells, is adapted to stimulate anabolic glycolysis–driven processes for incorporation of nutrients into nucleotides, amino acids and lipids to synthesize macromolecules required for growth and proliferation. We used a doxycycline–regulated Tet-On gene expression system to achieve controlled expression of MTG16. A noticeable finding was that the expression of genes for key glycolytic regulators involved in aerobic tumor cell glycolysis was diminished by MTG16.

2012-12-04 | GSE42682 | GEO

Expression data from murine Tet-off MLL-AF9/Ras acute myeloid leukemia cell lines following withdrawal of MLL-AF9

Project description:To explore oncogene addiction programs in a genetically defined leukemia context we developed an AML mouse model driven by a conditional MLL-AF9 allele together with oncogenic Ras, which enabled us to examine the consequences of MLL-AF9 inhibition in established disease. In order to produce a tightly regulated system that was easy to monitor, we constructed two retroviral vectors containing dsRed-linked MLL-AF9 under control of a tetracycline response element promoter, and KrasG12D or NrasG12D linked to the “Tet-off” tet-transactivator, which activates TRE expression in a doxycycline repressible manner. Leukemias were generated by retroviral cotransduction of both vectors into hematopoietic stem and progenitor cells, which were transplanted into syngeneic mice. Cells harboring both constructs induced aggressive myelomonocytic leukemia. Five independent primary leukemia cell lines were established from bone marrow of terminal mice. Treatment of these lines with doxycycline rapidly turned off MLL-AF9 expression, and induced terminal myeloid differentiation and complete disease remission in vivo. To identify molecular mechanisms underlying addiction to MLL-AF9, we analyzed global gene expression changes following doxycycline-induced suppression of MLL-AF9. Independent primary acute myeloid leukemia lines induced by cotransduction of Tet-off MLL-AF9 together with either KrasG12D or NrasG12D were grown in culture and treated with doxycycline for 6 days to inactivate MLL-AF9 expression. In addition, primary acute myeloid leukemia lines with constitutive MLL-AF9 and KrasG12D were included to control for the effects of doxycycline. Untreated and treated cells were harvested for RNA extraction and hybridization to Affymetrix arrays.

2011-08-04 | E-GEOD-30746 | biostudies-arrayexpress

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2016-06-29 | E-GEOD-68462 | biostudies-arrayexpress

Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors depends on IGF signaling

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2010-08-01 | E-GEOD-16684 | biostudies-arrayexpress

Expression data from Î²-globin let7 HeLa tet off cells treated with doxycycline

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2016-03-15 | E-GEOD-66541 | biostudies-arrayexpress

Effect of HIC1 and miR-212/132 expression on MCF7 cells

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Histone deacetylase 7 role in B cell acute lymphoblastic leukemia and B cell lymphoma

Project description:The generation of B cells is a complex process requiring several cellular transitions, including cell commitment and differentiation, that are tightly controlled by the action of linage-specific transcription factors. Proper transcriptional control to establish the genetic programs characteristic of each cellular stage is essential for the correct development of B lymphocytes. In fact, deregulation of these particular transcriptional programs may result in a block in B cell maturation, contributing to the development of hematological malignancies such as leukemia and lymphoma. In this experiments, We study the HDAC7 expression levels in pro-B-ALL and Burkitt lymphoma. SD-1 Tet-On-Tight-HDAC7 or SD-1 cells were treated or not for 24 hours with doxycycline. We compare the effects in gene expression between the different situations (in presence or in absence of doxycycline)

2014-12-18 | E-GEOD-51895 | biostudies-arrayexpress

Combinatorial targeting of glycolysis and oxidative phosphorylation suppresses tumor growth and metastases.

Project description:The Warburg effect, consisting of increased glucose uptake and glycolysis, provides metabolic energy as well as cellular building blocks for tumor growth. Inhibition of the Warburg effect with 2-deoxyglucose (2DG) has been explored in clinical trials with limited efficacy. Blockage of glycolysis can induce autopahgy resulting in alternative energy generation through oxidative phosphorylation providing a potential bypass of the effects of inhibition of glycolysis. Here in we demonstrate that activation of AMPK, as a consequence of energetic stress, induces mitochondrial energy production potentially bypassing the effects of glycolysis inhibition. We thus combined blockage of glycolysis by 2DG with inhibition of the electron transfer complex I (ETC1) in the mitochondria with the clinically applicable antidiabetic drug metformin. The combination resulted in activation of AMPK and autopahgy that however rendered eventual depletion of ATP and cell death. Furthermore, combined inhibition of glycolysis and mitochondrial respiration inhibited tumor growth and markedly decreased metastatic capacity in vivo. In order to understand the mechanism of these metabolic inhibitors, we performed whole genome transcriptional analysis. Human SK-4 esophageal cancer cell lines were treated with 5 different treatment groups [2 deoxy glucose (4mM), Metformin (5mM), AICAR (2mM), 2 deoxy glucose (4mM) plus Metformin (5mM) and 2 deoxy glucose (4mM) plus AICAR (2mM)] with non treated control groups for 12 hrs. Each groups was quadruplicated. Microarray experiments and data analysis were done at Dept. of Systems Biology, MDACC (Houston, USA)

2012-12-31 | E-GEOD-16816 | biostudies-arrayexpress

Expression data from murine acute myeloid leukemia (AML) cells following shRNA-mediated suppression of Myb

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2011-08-04 | E-GEOD-30745 | biostudies-arrayexpress

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