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. ORCID: https://orcid.org/0000-0001-7389-8673 and Watson, Christine J. 2003. A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland. Development 130 (15) , pp. 3459-3468. 10.1242/dev.00578

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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/EBP?, 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

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Uncontrolled Keywords:	LIF ; Mammary development ; STAT3 ; Apoptosis ; ERK ; Mouse
ISSN:	0950-1991
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/1010

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