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
em 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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Base de dados:
MEDLINE
Assunto principal:
Transativadores
/
Linfocinas
/
Interleucina-6
/
Apoptose
/
Regulação da Expressão Gênica no Desenvolvimento
/
Proteínas de Ligação a DNA
/
Inibidores do Crescimento
/
Glândulas Mamárias Animais
/
Proteínas do Leite
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article