Abstract:
:Intracellular signaling pathways present targets for pharmacological agents with potential for treatment of neoplastic diseases, with some disease remissions already recorded. However, cellular compensatory mechanisms usually negate the initial success. For instance, attempts to interrupt aberrant signaling downstream of the frequently mutated ras by inhibiting ERK1/2 has shown only limited usefulness for cancer therapy. Here, we examined how ERK5, that overlaps the functions of ERK1/2 in cell proliferation and survival, functions in a manner distinct from ERK1/2 in human AML cells induced to differentiate by 1,25D-dihydroxyvitamin D3 (1,25D). Using inhibitors of ERK1/2 and of MEK5/ERK5 at concentrations specific for each kinase in HL60 and U937 cells, we observed that selective inhibition of the kinase activity of ERK5, but not of ERK1/2, in the presence of 1,25D resulted in macrophage-like cell morphology and enhancement of phagocytic activity. Importantly, this was associated with increased expression of the macrophage colony stimulating factor receptor (M-CSFR), but was not seen when M-CSFR expression was knocked down. Interestingly, inhibition of ERK1/2 led to activation of ERK5 in these cells. Our results support the hypothesis that ERK5 negatively regulates the expression of M-CSFR, and thus has a restraining function on macrophage differentiation. The addition of pharmacological inhibitors of ERK5 may influence trials of differentiation therapy of AML.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Wang X,Pesakhov S,Harrison JS,Kafka M,Danilenko M,Studzinski GPdoi
10.1016/j.yexcr.2014.10.003subject
Has Abstractpub_date
2015-01-01 00:00:00pages
199-211issue
1eissn
0014-4827issn
1090-2422pii
S0014-4827(14)00442-Xjournal_volume
330pub_type
杂志文章abstract::The majority of human tumors are angiogenesis dependent. Understanding the specific mechanisms that contribute to angiogenesis may offer the best approach to develop therapies to inhibit angiogenesis in cancer. Endothelial monocyte activating polypeptide-II (EMAP-II) is an anti-angiogenic cytokine with potent effects ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2009.03.021
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abstract::Rabbit antisera prepared against embryonic chick liver cells have been characterized using cell cytotoxicity tests, antibody absorption tests, inhibition of cell-cell reaggregation and cell-aggregate adhesion assays. The sera contain antibodies which specifically block embryonic chick liver cell-cell aggregation with ...
journal_title:Experimental cell research
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doi:10.1016/0014-4827(82)90420-7
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abstract::The human neuroblastoma cell line SH-SY5Y can differentiate into a functional sympathetic neuronal phenotype when treated with low concentrations of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of serum or defined growth factors. When TrkA is introduced into the cells, NGF also induces ...
journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2008.12.022
更新日期:2009-05-01 00:00:00
abstract::The effect of 1 microM antimycin on the proliferative properties, metabolism and basic cell composition of Ehrlich ascites tumour cells cultured in the second in vitro passage was studied. Continuous drug exposure of asynchronous cells caused rapid cessation of cell growth, characterized by the cell number and DNA, RN...
journal_title:Experimental cell research
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doi:10.1016/0014-4827(85)90162-4
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abstract::Screening for microbial metabolites that induce transcriptional activation of the SV40 promoter resulted in the identification of two known compounds, FR901228 and trichostatin A (TSA). FR901228 is a potent antitumor drug that is currently under clinical investigation. TSA is a specific inhibitor of histone deacetylas...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1998.4027
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2003.11.017
更新日期:2004-03-10 00:00:00
abstract::Experiments are described which show that the torsional oscillations arising in a strand of the slime mould, Physarum polycephalum, under certain conditions remain closely correlated to oscillations in cytoplasmic streaming. When this is the case, the direction of rotation is related to the direction of streaming by a...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(83)90401-9
更新日期:1983-11-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2004.08.032
更新日期:2005-01-01 00:00:00
abstract::Activation of mouse bone marrow-derived mast cells (BMMC) by thrombin (0.05-0.5 U/million cells) resulted in a concentration-dependent release of histamine, which levelled off by 0.1 U thrombin. Rat peritoneal mast cells (RMC) were not stimulated by thrombin, though in control experiments, both types of mast cells deg...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90184-3
更新日期:1985-10-01 00:00:00
abstract::Rat glomerular epithelial cells were grown to confluency on semipermeable tissue culture inserts and the plasminogen system of these cells was analyzed using enzyme assays, Western analysis, zymography, and reverse transcriptase-PCR. The glomerular epithelial cells are capable of activating exogenous plasminogen to pl...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1995.1191
更新日期:1995-06-01 00:00:00
abstract::We evaluated cellular mechanisms involved in the activation pathway of matrix prometalloproteinase-2 (pro-MMP-2), an enzyme implicated in the malignant progression of many tumor types. Membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves the N-terminal prodomain of pro-MMP-2 thus generating the activation interm...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2000.5118
更新日期:2001-02-15 00:00:00
abstract::Human dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) derived from the ectomesenchymal tissue, have been shown to exhibit stem/progenitor cell properties and the ability to induce tissue regeneration. Stem cells in dental follicle differentiate into cementoblasts, periodontal ligament fibroblasts a...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2015.12.011
更新日期:2016-07-01 00:00:00
abstract::Paclitaxel (Taxol) has been successfully combined with the monoclonal antibody trastuzumab (Herceptin) in the treatment of ErbB2 overexpressing cancers. However, this combination therapy showed an unexpected synergistic increase in cardiac dysfunction. We have studied the mechanisms of paclitaxel/anti-ErbB2 cardiotoxi...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2007.02.007
更新日期:2007-05-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2014.09.031
更新日期:2015-01-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2014.07.001
更新日期:2014-10-01 00:00:00
abstract::Chondrocytes express CD44 as a primary receptor for the matrix macromolecule hyaluronan. Hyaluronan is responsible for the retention and organization of proteoglycan within cartilage, and hyaluronan-chondrocyte interactions are important for the assembly and maintenance of the cartilage matrix. Bovine articular chondr...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1999.4641
更新日期:1999-11-01 00:00:00
abstract::It has been generally accepted that alternatively activated macrophages (M2), which can be induced by type 2 cytokines such as IL-4, is responsible for tissue repair. However, the function of JNK in IL-4-induced M2 macrophage polarization remains unclear. Here, we demonstrated that M0 macrophages can be polarized into...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2017.05.010
更新日期:2017-08-15 00:00:00
abstract::Filamin is a well-characterized actin-associated protein first isolated from chicken smooth muscle. Subsequently, this polypeptide and its nonmuscle homolog actin-binding protein have been shown to be expressed in avian muscle tissue, mammalian smooth muscle, mammalian macrophages and other blood cell types, as well a...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1993.1317
更新日期:1993-12-01 00:00:00
abstract::In human and non-human primates, migratory trophoblasts penetrate the uterine epithelium, invade the endometrium, enter the uterine vasculature, and migrate within the arteries. The mechanisms that regulate this directional migration are unknown. We have used early gestation macaque trophoblasts to test the hypothesis...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2005.01.013
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90084-9
更新日期:1985-12-01 00:00:00
abstract::Pluripotent stem cell activity is essential to maintain regeneration and homeostasis in the Drosophila midgut following environmental challenges. Although multiple pathways have been implicated in epithelial renewal, the underlying regulatory mechanisms and correlations between relevant genes and pathways remain elusi...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2017.10.021
更新日期:2017-12-15 00:00:00
abstract::Sperm cells from control donors of proven fertility and men from barren couples were studied by conventional procedures, i.e., light microscopy as well as flow cytometry. Light microscopy analysis of semen included the measurement of spermatozoa concentration, morphology, and motility. All the men from barren couples ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1998.4064
更新日期:1998-06-15 00:00:00
abstract::The measurement of chromomycin A3/DAPI fluorescence ratios is shown to allow base content determinations in eu- and heterochromatic regions of interphase cell nuclei. The base content values obtained in chromocenters and euchromatin of Scilla sibirica agree with those measured earlier [12] on the band and non-band are...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(83)90223-9
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abstract::Incubation of isolated rat hepatocytes under conditions which support maximal autophagy (amino acid-free medium) caused a marked alteration in the density distribution of lysosomes in continuous metrizamide gradients (mean peak density reduced from 1.14 to 1.09 g/ml). The autophagic sequestration inhibitor 3-methylade...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90141-7
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abstract::Sendai virus (SV) glycoproteins were co-reconstituted with the erythrocyte membrane polypeptide designated as band 3 (B3). Fusion of the hybrid vesicles, SV-B3, with L, HeLa and Friend erythroleukemic (FEL) cells led to fusion-mediated implantation of the erythrocyte band 3 into the plasma membranes of the above cells...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(83)90190-8
更新日期:1983-10-01 00:00:00
abstract::Cytoplasts derived from senescent and quiescent human diploid cells inhibit DNA synthesis initiation when fused with cells capable of proliferation. When the cytoplasts were subjected to a variety of conditions (trypsin and cycloheximide treatment and growth on fibronectin), this inhibitory activity was lost, suggesti...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90177-6
更新日期:1985-10-01 00:00:00
abstract::The biosynthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH4) in murine erythroleukemia (MEL) cells is almost completely inhibited by 10 mM, 2,4-diamino-6-hydroxypyrimidine (DAHP), which targets GTP cyclohydrolase. The inhibition results in dephosphorylation of the retinoblastoma gene product, prolongation of the G1-phas...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1996.0021
更新日期:1996-01-10 00:00:00
abstract::Mesenchymal stem cells are universally regarded across many fields of medicine, as one of the most promising cell types for use in cell-based therapies. Although not yet fully understood, the therapeutic effects of these cells are largely attributed to the trophic actions of growth factors and cytokines present in the...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2014.12.019
更新日期:2015-04-10 00:00:00