Tumor necrosis factor alpha induces LIF expression through ERK1/2 activation in mammary epithelial cells
| Autor: | Matías Blaustein, Carolina Schere Levy, Omar A. Coso, Victoria Slomiansky, Albana Gattelli, Federico Pelisch, Edith C. Kordon, Karen Nahmod, Anabella Srebrow |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Blotting Western Electrophoretic Mobility Shift Assay Biology Leukemia Inhibitory Factor Biochemistry Cell Line Mice Internal medicine medicine Animals Humans Involution (medicine) Mammary Glands Human Molecular Biology Mammary gland involution Transcription factor Mitogen-Activated Protein Kinase 1 Mice Inbred BALB C Mitogen-Activated Protein Kinase 3 Tumor Necrosis Factor-alpha Cell Biology Immunohistochemistry Enzyme Activation Transcription Factor AP-1 AP-1 transcription factor Endocrinology Cytokine Cancer research Tumor necrosis factor alpha Signal transduction Leukemia inhibitory factor |
| Zdroj: | Journal of Cellular Biochemistry. 110:857-865 |
| ISSN: | 0730-2312 |
| Popis: | It has been reported that expression of tumor necrosis factor superfamily members occur at the onset of the mammary gland post-lactational involution. One of these proteins, tumor necrosis factor alpha (TNFalpha), is a major mediator of inflammation that is able to induce expression of several cytokines. Leukemia inhibitory factor (LIF) is an inflammatory cytokine that is induced and plays a fundamental role during post-lactational involution of the mammary gland. Therefore, our goal was to determine whether TNFalpha activity in the mammary epithelium might include regulation of LIF expression. This biological role would increase the significance of TNFalpha expression at the end of lactation. Our results show that TNFalpha was able to induce LIF transcription through ERK1/2 activation in a non-tumorigenic mouse mammary epithelial cell line, SCp2. We found that activation of TNFalpha receptor-2 (TNFR2) was specifically involved in triggering this signaling pathway. In addition, our data suggest the participation of AP-1 transcription factor family members in this pathway. We determined that TNFalpha treatment induced c-fos transcription, and blocking AP-1 activity resulted in a significant inhibition of TNFalpha-induced LIF expression. Finally, we found that TNFalpha was also able to trigger LIF expression and ERK1/2 activation in the mouse mammary gland in vivo. Therefore, our data suggest that TNFalpha may contribute to mammary gland involution by, among other activities, eliciting LIF expression through ERK1/2 and AP1 activation. |
| Databáze: | OpenAIRE |
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