A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland.
Development
; 130(15): 3459-68, 2003 Aug.
Article
in En
| MEDLINE
| ID: mdl-12810593
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trans-Activators
/
Lymphokines
/
Interleukin-6
/
Apoptosis
/
Gene Expression Regulation, Developmental
/
DNA-Binding Proteins
/
Growth Inhibitors
/
Mammary Glands, Animal
/
Milk Proteins
Language:
En
Journal:
Development
Journal subject:
BIOLOGIA
/
EMBRIOLOGIA
Year:
2003
Document type:
Article
Affiliation country:
United kingdom
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM