Calcium Induces Cell Survival and Proliferation through the Activation of the MAPK Pathway in a Human Hormone-dependent Leukemia Cell Line, TF-1
| Autor: | Judit Jánossy, Pal I. Bauer, Mária Magócsi, Ágota Apáti, Anna Brózik |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
MAPK/ERK pathway
Programmed cell death Time Factors Transcription Genetic Cell Survival MAP Kinase Signaling System medicine.medical_treatment Blotting Western Antigens CD34 Apoptosis Biology Biochemistry chemistry.chemical_compound Tumor Cells Cultured medicine Humans Enzyme Inhibitors Phosphorylation Molecular Biology Cell Nucleus Flavonoids Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Cell Death Caspase 3 Cell growth Kinase Ionomycin Cell Cycle Granulocyte-Macrophage Colony-Stimulating Factor Cell Biology Cell cycle Cell biology Transcription Factor AP-1 Cytokine Proto-Oncogene Proteins c-bcl-2 chemistry Caspases Calcium Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-fos Cell Division |
| Zdroj: | Journal of Biological Chemistry. 278:9235-9243 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m205528200 |
| Popis: | Survival and proliferation of cells of a human myelo-erythroid CD34+ leukemia cell line (TF-1) depend on the presence of granulocyte-macrophage colony-stimulating factor or interleukin-3. Upon hormone withdrawal these cells stop proliferating and undergo apoptotic process. In this report we demonstrate that a controlled increase in [Ca2+]i induces hormone-independent survival and proliferation of TF-1 cells. We found that moderate elevation of [Ca2+]i by the addition of cyclopiasonic-acid protected TF1 cells from apoptosis. Furthermore, a higher, but transient elevation of [Ca2+]i by ionomycin treatment induced cell proliferation. In both cases caspase-3 activity was reduced, and Bcl-2 was up-regulated. Higher elevation of [Ca2+]i by ionomycin induced MEK-dependent biphasic ERK1/2 activation, sufficient to move the cells from G0/G1 to S/M phases. Meanwhile, activation of ERK1/2, phosphorylation of the Elk-1 transcription factor, and, consequently, a substantial elevation of Egr-1 and c-Fos levels and AP-1 DNA binding were observed. Moderate elevation of [Ca2+]i, on the other hand, caused a delayed monophasic activation of ERK1/2 and Elk-1 that was accompanied with only a small increase of Egr-1 and c-Fos levels and AP-1 DNA binding. The specific MEK-1 kinase inhibitor, PD98059, inhibited all the effects of increasing [Ca2+]i, indicating that the MAPK/ERK pathway activation is essential for TF-1 cell survival and proliferation. Based on these results we suggest that the elevation of the [Ca2+]i may influence the cytokine dependence of hemopoietic progenitors and may contribute to pathological hematopoiesis. |
| Databáze: | OpenAIRE |
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