Gene expression in Trp53 and Rb1 double knockout mouse prostate epithelial cancer cells expressing PIM1
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118786 | GEO | 2018/08/21
REPOSITORIES: GEO
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Project description:Gene expression in Trp53 and Rb1 double knockout mouse prostate epithelial cancer cells expressing PIM1
| PRJNA486800 | ENA
Project description:We used control and PIM1 over-expressing LNCaP cells to analyze the effect of PIM1 on gene expression. We find that PIM1 over-expression results in up- and down-regulation of different classes of genes, including increasing gene expression involved in extracellular matrix organization, cell adhesion, and cytokine signaling.
2021-11-03 | GSE181225 | GEO
Project description:Background: PIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity. Methods: Pim1-/-MAEC were isolated from Pim1 knockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis. Results: Pim1-/-MAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of Pim1- cDNA into Pim1-/-MAEC significantly restored wildtype adhesive characteristics. Pim1-/--MAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and M-NM-2-catenin, respectively. Junctional molecules such as Cadherin 13 and matrix components such as Collagen 6a3 were highly upregulated in Pim1-/- cells. Intriguingly, extracellular matrix deposited by Pim1-/- cells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells. Conclusion: Loss of Pim1 induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity. Pim-1-/- mouse aortic endothelial cells were compared to wildtype cells
2012-10-29 | E-GEOD-32059 | biostudies-arrayexpress
Project description:PIM1 is an oncogenic serine/threonine kinase that promotes and maintains prostate
tumorigenesis. To more fully understand the mechanism by which PIM1 promotes oncogenesis,
we performed a chemical genetic screen to identify direct PIM1 substrates in prostate cancer
cells. To identify PIM1 substrates and their phosphorylation sites in LNCaP cells, we coupled a
chemical genetic screen with a peptide capture, mass spectrometry (MS)-based approach. We
mutated the PIM1 gatekeeper residue in the ATP binding site to accept a bulky ATP analog. By
using an ATP analog labeled with a thiol group on the gamma-phosphate, we were able specifically
label PIM1 substrates even in the presence of other cellular kinases.
2020-02-27 | MSV000085028 | MassIVE
Project description:It has been estimated that about 11% of cellular genes present a functional E box to which MYC can associate on the genome. MYC silencing demonstrated that MYC recruits PIM1 at specific MYC binding sites and confocal microscopy following growth factor treatment, showed an elevated degree of nuclear co-localization of PIM1 with nascent transcripts and with MYC suggesting that PIM1 is recruited by MYC to a large number of sites. To understand the actual extension of PIM1 and MYC co-operation in gene transcription we performed expression profile analysis of 293 cells silenced either for MYC or PIM1 at 120 minutes after serum treatment. MYC silencing affected the expression of 1026 genes of which 818 were up-regulated and 208 were down-regulated. Comparison of genes regulated by MYC with those regulated by PIM1, by RNAi silencing, showed that PIM1 contributes to the regulation of 207 genes out of the 1026 MYC-regulated genes. Thus, a subset of 20% of MYC-regulated genes, are also regulated by PIM1. The co-regulated includes genes involved in cell metabolism, protein synthesis, cycle progression, and oncogenesis. Interestingly, a large number of genes are transcriptional factors, which suggests that PIM1 participates in MYC-dependent regulatory networks. Experiment Overall Design: The gene expression analysis was performed by hybridizing RNA samples to the Whole Human Genome Oligo Microarray from Agilent Technologies. Samples were obtained from 293 cells, treated with serum for 120 minutes, expressing either two independent MYC shRNA (shMYC#1 and shMYC#2) or their relative scrambled shRNA (shsM#1 and shsM#2) for MYC expression analysis; two independent PIM1 shRNA (shPIM1#1 and shPIM1#2) or their relative scrambled shRNA (shsP#1 and shsP#2) for PIM1 expression analysis.
2008-06-15 | E-GEOD-7960 | biostudies-arrayexpress
Project description:It has been estimated that about 11% of cellular genes present a functional E box to which MYC can associate on the genome. MYC silencing demonstrated that MYC recruits PIM1 at specific MYC binding sites and confocal microscopy following growth factor treatment, showed an elevated degree of nuclear co-localization of PIM1 with nascent transcripts and with MYC suggesting that PIM1 is recruited by MYC to a large number of sites. To understand the actual extension of PIM1 and MYC co-operation in gene transcription we performed expression profile analysis of 293 cells silenced either for MYC or PIM1 at 120 minutes after serum treatment. MYC silencing affected the expression of 1026 genes of which 818 were up-regulated and 208 were down-regulated. Comparison of genes regulated by MYC with those regulated by PIM1, by RNAi silencing, showed that PIM1 contributes to the regulation of 207 genes out of the 1026 MYC-regulated genes. Thus, a subset of 20% of MYC-regulated genes, are also regulated by PIM1. The co-regulated includes genes involved in cell metabolism, protein synthesis, cycle progression, and oncogenesis. Interestingly, a large number of genes are transcriptional factors, which suggests that PIM1 participates in MYC-dependent regulatory networks. Keywords: expression profiles
2007-07-31 | GSE7960 | GEO
Project description:Background: PIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity. Methods: Pim1-/-MAEC were isolated from Pim1 knockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis. Results: Pim1-/-MAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of Pim1- cDNA into Pim1-/-MAEC significantly restored wildtype adhesive characteristics. Pim1-/--MAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and β-catenin, respectively. Junctional molecules such as Cadherin 13 and matrix components such as Collagen 6a3 were highly upregulated in Pim1-/- cells. Intriguingly, extracellular matrix deposited by Pim1-/- cells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells. Conclusion: Loss of Pim1 induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity.
2012-10-29 | GSE32059 | GEO
Project description:The Pim (proviral integration site for Moloney murine leukemia virus) proteins form a serine threonine kinase family that regulates cell proliferation, migration and cell survival. Here we demonstrate for the first time that a Pim1 kinase plays an essential role in antiviral innate immune responses. Specifically, our in vivo, in vitro and RNA-sequencing analyses showed that Pim1 was quickly upregulated after Toll-like receptor (TLR) stimulation in a NF-kB-dependent manner and then promoted IFN-b production by forming a cell-surface complex composed of TRIF-signaling molecules and IRF3 that promoted IRF3 phosphorylation, nuclear translocation, and IFN-b production. As shown by Pim1 knockdown and knockout, Pim1 was essential for this role but its kinase activity was not involved. Pim1-deficiency increased the susceptibility of mice to poly I:C-induced sepsis. Our study uncovers a previously unrecognized role for Pim1 in antiviral innate immune responses, thus providing a new target for controlling viral infection.
2022-12-14 | GSE195582 | GEO
Project description:Human prostate cancer LNCaP cells infected with Lentivirus carried huamn BRCA2 gRNA alone or in combination with lentivirus carrying human RB1 shRNA. Infected cell were selcted by drug selection and the knockdown were confirm by westernblot or qPCR
2020-05-07 | GSE114153 | GEO
Project description:Myelofibrosis (MF) is the deadliest form of myeloproliferative neoplasm (MPN). Pim1 expression is significantly elevated in MPN/MF hematopoietic progenitors. So, we investigated the role of Pim1 in myelofibrosis. We show that genetic ablation of Pim1 blocked the development of myelofibrosis induced by Jak2V617F and MPLW515L. Pharmacologic inhibition of Pim1 with a second-generation Pim kinase inhibitor TP-3654 significantly reduced leukocytosis, splenomegaly and attenuated bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of MF. Combined treatment of TP-3654 and Ruxolitinib resulted in greater reduction of spleen size, normalization of blood leukocyte counts and abrogation of bone marrow fibrosis in murine models of MF. TP-3654 treatment also preferentially inhibited Jak2V617F mutant hematopoietic progenitors in mice. Our results suggest that Pim1 plays an important role in the pathogenesis of MF, and inhibition of Pim1 with TP-3654 might be useful for treatment of MF.
2022-07-01 | GSE183467 | GEO