The role of ABL kinases in medulloblastoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA932216 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23357752_1.fastq.gz | Fastqsanger.gz | |||
| SRR23357752_2.fastq.gz | Fastqsanger.gz | |||
| SRR23357753_1.fastq.gz | Fastqsanger.gz | |||
| SRR23357753_2.fastq.gz | Fastqsanger.gz | |||
| SRR23357754_1.fastq.gz | Fastqsanger.gz |
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Project description:Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD in medulloblastoma are largely unclear. The Abelson (ABL) family of non-receptor tyrosine kinases has been implicated in cancer cell migration, invasion, adhesion, and chemotherapy resistance, and these kinases are upstream mediators of the oncogene c-MYC in fibroblasts. However, their role in medulloblastoma has not yet been explored. Therefore, the purpose of this work is to elucidate the role of the ABL kinases, ABL1 and ABL2, in medulloblastoma LMD. We show here that ABL1/2 mRNA is highly expressed in human medulloblastoma tumor samples and cell lines and that pharmacologic inhibition of ABL kinases results in medulloblastoma cell death. Knockdown of the ABL kinase genes ABL1 and ABL2 results in decreased adhesion to the extracellular matrix protein, vitronectin, and decreased medulloblastoma proliferation in a mouse model of medulloblastoma LMD (resulting in decreased tumor burden with subsequent increased overall survival. Further, both pharmacologic inhibition of ABL1/2 and ABL1/2 knockdown resulted in decreased c-myc expression, revealing a putative signaling pathway. In summary, this work highlights the potential role of ABL kinases in medulloblastoma LMD via c-myc expression.
2023-10-04 | GSE224691 | GEO
Project description:To gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent bone metastasis, we evaluated the consequences of single or double inactivation of ABL1 and ABL2 on the transcriptome of breast cancer cells. Double ABL1/ABL2 knockdown was required to decrease the levels of p-CrKL by more than 90%, indicative of inactivation of the endogenous ABL kinases. To examine the consequences of depleting the ABL kinases on the transcriptome of metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 180 genes were significantly down-regulated and 40 genes were significantly up-regulated in ABL1/ABL2 knockdown cells. Four samples were analyzed control, Abl single knockdown, Arg single knockdown, Abl/Arg double knockdown. Experiments were performed in triplicate.
2016-03-02 | E-GEOD-69125 | biostudies-arrayexpress
Project description:To gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent bone metastasis, we evaluated the consequences of single or double inactivation of ABL1 and ABL2 on the transcriptome of breast cancer cells. Double ABL1/ABL2 knockdown was required to decrease the levels of p-CrKL by more than 90%, indicative of inactivation of the endogenous ABL kinases. To examine the consequences of depleting the ABL kinases on the transcriptome of metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 180 genes were significantly down-regulated and 40 genes were significantly up-regulated in ABL1/ABL2 knockdown cells.
2016-03-02 | GSE69125 | GEO
Project description:To gain insight into the signaling pathway(s) required for ABL1/ABL2-kinase activity or effected by Ponatinib treatment, we evaluated the consequences of single or double inactivation of ABL1/ABL2 cells, or Ponatinib treated cells on the transcriptome of breast cancer cells. To examine the consequences of depleting the ABL kinases, or Ponatinib treatment on the transcriptome of lung metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 321 genes were significantly differently expressed in Ponatinib treated LM2 cells, and 73 genes were differently expressed in double inactivation of ABL1/ABL2 LM2 cells. However, only about 3.4 percent of Ponatinib affected genes can also be changed by ABL knocking down.
2018-03-01 | GSE95079 | GEO
Project description:Abl kinases, which are required for multiple cellular processes, including proliferation, apoptosis, adhesion, cell migration, and stress responses, widely participate in the regulation of gene transcription. To illustrate the role of Abl kinase in gene expression, the transcription of approximately 22,000 genes in wild-type (WT) and c-abl/arg knockout MEFs was detected using Affymetrix GeneChips (Mouse Genome 430 2.0).
2021-01-14 | GSE154568 | GEO
Project description:Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGF-beta-R and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dcl3 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. Keywords: comparative gene expression analysis
2008-07-12 | GSE11794 | GEO
Project description:Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGF-beta-R and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dcl3 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. Experiment Overall Design: In our microarray study, we have total 22 samples from four different cell lines expressing BCR-ABL, TEL-ABL, FLT3-ITD or TEL-PDGF-betaR. Each cell line was treated with specific small molecule inhibitors for 4 hours, then RNA was extracted and cRNA was hybridized to Affymetrix U74 oligonucleotide arrays. Untreated cells or cells treated with unrelated inhibitors were used as controls or references. We have three replicates and six references obtained from three independent experiments for cells expressing BCR-ABL or FLT3-ITD. We have one treated and one untreated sample for each cell line expressing TEL-ABL or TEL-PDGF-beta-R.
2008-10-21 | E-GEOD-11794 | biostudies-arrayexpress
Project description:Using a mouse model of chronic myelogenous leukemia (CML), here we report that HIF1α plays a crucial role in survival maintenance of leukemia stem cells (LSCs). Deletion of HIF1α impairs the propagation of CML through impairing cell cycle progression and inducing apoptosis of LSCs. Deletion of HIF1α results in elevated expression of p16Ink4a and p19Arf in LSCs, and knockdown of p16Ink4a and p19Arf rescues the defective colony-forming ability of HIF1α-/- LSCs. To further identify the pathways in which Hif1a regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Hif1a-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+ cells, BCR-ABL-expressing wild type LSCs, and BCR-ABL-expressing Hif1a-/- LSCs.
2012-04-04 | GSE35111 | GEO
Project description:Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell, characterized by the expression of the Bcr-Abl oncogene by leukemic cells. In order to analyze the molecular pathways modulated by Bcr-Abl, we have previously generated an inducible model of Bcr-Abl expression in the murine Ba/F3 cell line based on the Tet-OFF system. In the present study, through a microarray approach applied to cells grown with (Bcr-Abl-expression OFF) or without (Bcr-Abl-expression ON) doxycycline, a tetracycline analogue, we analyzed the gene expression variations upon Bcr-Abl expression. Keywords: repeat sample
2005-05-01 | GSE1429 | GEO
Project description:Using a mouse model of chronic myelogenous leukemia (CML), here we report that HIF1M-NM-1 plays a crucial role in survival maintenance of leukemia stem cells (LSCs). Deletion of HIF1M-NM-1 impairs the propagation of CML through impairing cell cycle progression and inducing apoptosis of LSCs. Deletion of HIF1M-NM-1 results in elevated expression of p16Ink4a and p19Arf in LSCs, and knockdown of p16Ink4a and p19Arf rescues the defective colony-forming ability of HIF1M-NM-1-/- LSCs. To further identify the pathways in which Hif1a regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Hif1a-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+ cells, BCR-ABL-expressing wild type LSCs, and BCR-ABL-expressing Hif1a-/- LSCs. To identify genes that are regulated by BCR-ABL in LSCs and LSCs without the Hif1a gene, we compared the gene profile between wild type (WT) LSCs and Hif1a-/- LSCs.
2012-04-03 | E-GEOD-35111 | biostudies-arrayexpress