Leukemia inhibitory factor induces apoptosis of the mammary epithelial cells and participates in mouse mammary gland involution.
Leukemia inhibitory factor (LIF) is a multifunctional glycoprotein that displays multiple biological activities in different cell types, but to date there has been no report on its expression in the normal mammary gland. In this study we found that LIF is expressed at low but detectable levels in postpubertal, adult virgin, and pregnant mouse mammary glands. However, LIF expression drops after parturition to become almost undetectable in lactating glands. Interestingly, LIF expression shows a steep increase shortly after weaning that is maintained for the following 3 days. During this period, known as the first stage of mammary gland involution, the lack of suckling induces local factors that cause extensive epithelial cell death. It has been shown that Stat3 is the main factor in signaling the initiation of apoptosis, but the mechanism of its activation remains unclear. Herein, we show that LIF expression in the gland is induced by milk stasis and not by the decrease of circulating lactogenic hormones after weaning. Implantation of LIF containing pellets in lactating glands results in a significant increase in epithelium apoptosis. In addition, this treatment also induces Stat3 phosphorylation. We conclude that LIF regulated expression in the mouse mammary gland may play a relevant role during the first stage of mammary gland involution. Our results also show that LIF-induced mammary epithelium apoptosis could be mediated, at least partially, by Stat3 activation.
Schere-Levy
Carolina
C
ILEX-CONICET División de Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Buggiano
Valeria
V
Quaglino
Ana
A
Gattelli
Albana
A
Cirio
Maria Cecilia
MC
Piazzon
Isabel
I
Vanzulli
Silvia
S
Kordon
Edith C
EC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6; D007774:Lactation / Q000187:drug effects / Q000502:physiology*; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics; D053606:Receptors, OSM-LIF; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators