A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland.
AuthorsKritikou, Ekaterini A
Came, Paul J
Clarkson, Richard W E
Watson, Christine J
AffiliationDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
MetadataShow full item record
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.
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 Development
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- Authors: Haas CA, Hofmann HD, Kirsch M
- Issue date: 1999 Dec
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- Authors: Halfter H, Friedrich M, Postert C, Ringelstein EB, Stögbauer F
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- Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M.
- Authors: Schrell UM, Koch HU, Marschalek R, Schrauzer T, Anders M, Adams E, Fahlbusch R
- Issue date: 1998 Mar
- Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation.
- Authors: Cheng JG, Chen JR, Hernandez L, Alvord WG, Stewart CL
- Issue date: 2001 Jul 17