| A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland. | |
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MedLine Citation:
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PMID: 12810593 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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STAT3 is the key mediator of apoptosis in mammary gland. We demonstrate here that LIF is the physiological activator of STAT3, because in involuting mammary glands of Lif(-/-) mice, pSTAT3 is absent and the STAT3 target, C/EBPdelta, is not upregulated. Similar to Stat3 knockouts, Lif(-/-) mammary glands exhibit delayed involution, reduced apoptosis and elevated levels of p53. Significantly, Lif(-/-) glands display precocious development during pregnancy, when pSTAT3 is not normally detected. We show that pERK1/2 is significantly reduced in Lif(-/-) glands at this time, suggesting that at this stage LIF mediates its effects through pERK1/2. Inhibition of LIF-mediated ERK1/2 phosphorylation potentiates the proapoptotic effects of STAT3. LIF therefore signals alternately through ERK1/2, then STAT3, to regulate mammary growth and apoptosis. |
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Authors:
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Ekaterini A Kritikou; Andrew Sharkey; Kathrine Abell; Paul J Came; Elizabeth Anderson; Richard W E Clarkson; Christine J Watson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 130 ISSN: 0950-1991 ISO Abbreviation: Development Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-06-17 Completed Date: 2003-09-03 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 3459-68 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, physiology* Butadienes / pharmacology Caseins / biosynthesis, genetics DNA-Binding Proteins / biosynthesis, genetics, metabolism* Female Gene Expression Regulation, Developmental / physiology* Growth Inhibitors / deficiency, genetics, metabolism* Interleukin-6* Leukemia Inhibitory Factor Leukemia Inhibitory Factor Receptor alpha Subunit Lymphokines / deficiency, genetics, metabolism* MAP Kinase Kinase 1 Mammary Glands, Animal / drug effects, embryology, metabolism* Mice Milk Proteins* Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Neural Cell Adhesion Molecules / biosynthesis, genetics Nitriles / pharmacology Protein-Serine-Threonine Kinases / antagonists & inhibitors Receptors, Cytokine / biosynthesis, genetics Receptors, OSM-LIF Receptors, Progesterone / metabolism STAT1 Transcription Factor STAT3 Transcription Factor STAT5 Transcription Factor Trans-Activators / biosynthesis, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Butadienes; 0/Caseins; 0/DNA-Binding Proteins; 0/Growth Inhibitors; 0/Interleukin-6; 0/Leukemia Inhibitory Factor; 0/Leukemia Inhibitory Factor Receptor alpha Subunit; 0/Lif protein, mouse; 0/Lifr protein, mouse; 0/Lymphokines; 0/Milk Proteins; 0/Neural Cell Adhesion Molecules; 0/Nitriles; 0/Receptors, Cytokine; 0/Receptors, OSM-LIF; 0/Receptors, Progesterone; 0/STAT1 Transcription Factor; 0/STAT3 Transcription Factor; 0/STAT5 Transcription Factor; 0/Stat1 protein, mouse; 0/Stat3 protein, mouse; 0/Trans-Activators; 0/U 0126; 0/cell adhesion molecule F11; EC 2.7.1.-/Map2k1 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.12.2/MAP Kinase Kinase 1; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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