STAT5 transcriptional activity is impaired by LIF in a mammary epithelial cell line.
Gene regulation mediated by STAT factors has been implicated in cellular functions with relevance to a variety of processes. Particularly, STAT5 and STAT3 play a crucial role in mammary epithelium displaying reciprocal activation kinetics during pregnancy, lactation and involution. Here, we show that LIF treatment of mammary epithelial HC11 cells reduces the phosphorylation levels and transcriptional activity of p-STAT5 in correlation with STAT3 phosphorylation. We have also found that STAT5 activity is negatively modulated by this cytokine, both on a gene whose expression is induced, as well as on a promoter repressed by STAT5. Besides, our results show that lactogenic hormones increase LIF effect on gene induction without modifying STAT3 phosphorylation state. Our findings strongly suggest that there is crosstalk between STAT5 and STAT3 pathways that could modulate their ability to regulate gene expression.
Granillo
Agustina Rodriguez
AR
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab. II, Piso 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
Boffi
Juan Carlos
JC
Barañao
Lino
L
Kordon
Edith
E
Pecci
Adali
A
Guberman
Alejandra
A
D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor / Q000502:physiology*; D008321:Mammary Glands, Animal; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D050799:STAT5 Transcription Factor / Q000502:physiology*; D051020:bcl-X Protein / Q000235:genetics
C494812:Bcl2l1 protein, mouse; D007328:Insulin; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D051020:bcl-X Protein; D051743:CCAAT-Enhancer-Binding Protein-delta; D003907:Dexamethasone; D011388:Prolactin