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
|
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: | Schools > Biosciences Research Institutes & Centres > 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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