A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82130
Title:
A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland.
Authors:
Kritikou, Ekaterini A; Sharkey, Andrew; Abell, Kathrine; Came, Paul J; Anderson, Elizabeth; Clarkson, Richard W E; Watson, Christine J
Abstract:
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.
Affiliation:
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Citation:
A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland. 2003, 130 (15):3459-68 Development
Journal:
Development
Issue Date:
Aug-2003
URI:
http://hdl.handle.net/10541/82130
DOI:
10.1242/dev.00578
PubMed ID:
12810593
Type:
Article
Language:
en
ISSN:
0950-1991
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKritikou, Ekaterini A-
dc.contributor.authorSharkey, Andrew-
dc.contributor.authorAbell, Kathrine-
dc.contributor.authorCame, Paul J-
dc.contributor.authorAnderson, Elizabeth-
dc.contributor.authorClarkson, Richard W E-
dc.contributor.authorWatson, Christine J-
dc.date.accessioned2009-09-22T15:56:42Z-
dc.date.available2009-09-22T15:56:42Z-
dc.date.issued2003-08-
dc.identifier.citationA dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland. 2003, 130 (15):3459-68 Developmenten
dc.identifier.issn0950-1991-
dc.identifier.pmid12810593-
dc.identifier.doi10.1242/dev.00578-
dc.identifier.urihttp://hdl.handle.net/10541/82130-
dc.description.abstractSTAT3 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.en
dc.language.isoenen
dc.subjectLeukaemia Inhibitory Factoren
dc.subjectLeukaemia Inhibitory Factor Receptor alpha Subuniten
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshButadienes-
dc.subject.meshCaseins-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation, Developmental-
dc.subject.meshGrowth Inhibitors-
dc.subject.meshInterleukin-6-
dc.subject.meshLeukemia Inhibitory Factor-
dc.subject.meshLeukemia Inhibitory Factor Receptor alpha Subunit-
dc.subject.meshLymphokines-
dc.subject.meshMAP Kinase Kinase 1-
dc.subject.meshMammary Glands, Animal-
dc.subject.meshMice-
dc.subject.meshMilk Proteins-
dc.subject.meshMitogen-Activated Protein Kinase Kinases-
dc.subject.meshNeural Cell Adhesion Molecules-
dc.subject.meshNitriles-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshReceptors, Cytokine-
dc.subject.meshReceptors, OSM-LIF-
dc.subject.meshReceptors, Progesterone-
dc.subject.meshSTAT1 Transcription Factor-
dc.subject.meshSTAT3 Transcription Factor-
dc.subject.meshSTAT5 Transcription Factor-
dc.subject.meshTrans-Activators-
dc.titleA dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.en
dc.identifier.journalDevelopmenten
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