title: Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland.
abstract: BACKGROUND
  Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals.
  
  
  RESULTS
  We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated) Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland.
  
  
  CONCLUSIONS
  Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland.
authors: Department of Immunology, University of Manitoba, Winnipeg, Canada ; Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada.
authors: Sumanta
authors: S
authors: Chatterjee
authors: Biological Sciences Platform, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Stephanie
authors: S
authors: Bacopulos
authors: Biological Sciences Platform, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Wenyi
authors: W
authors: Yang
authors: Biological Sciences Platform, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Yutaka
authors: Y
authors: Amemiya
authors: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors: Demetri
authors: D
authors: Spyropoulos
authors: Department of Immunology, University of Manitoba, Winnipeg, Canada ; Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada.
authors: Afshin
authors: A
authors: Raouf
authors: Biological Sciences Platform, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Arun
authors: A
authors: Seth
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018969:Insulin-Like Growth Factor Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000196:embryology / Q000473:pathology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; C102529:insulin-like growth factor binding protein-related protein 1