A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland.
Kritikou, Ekaterini A Sharkey, Andrew Abell, Kathrine Came, Paul J Anderson, Elizabeth Clarkson, Richard W E Watson, Christine J
Kritikou, Ekaterini A
Sharkey, Andrew
Abell, Kathrine
Came, Paul J
Anderson, Elizabeth
Clarkson, Richard W E
Watson, Christine J
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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.
Description
Date
2003-08
Publisher
Collections
Keywords
Leukaemia Inhibitory Factor
Leukaemia Inhibitory Factor Receptor alpha Subunit
Leukaemia Inhibitory Factor Receptor alpha Subunit
Type
Article
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