title: Ltbp1L is focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution.
abstract: BACKGROUND
  Latent TGFβ binding proteins (LTBPs) govern TGFβ presentation and activation and are important for elastogenesis. Although TGFβ is well-known as a tumor suppressor and metastasis promoter, and LTBP1 is elevated in two distinct breast cancer metastasis signatures, LTBPs have not been studied in the normal mammary gland.
  
  
  METHODS
  To address this we have examined Ltbp1 promoter activity throughout mammary development using an Ltbp1L-LacZ reporter as well as expression of both Ltbp1L and 1S mRNA and protein by qRT-PCR, immunofluorescence and flow cytometry.
  
  
  RESULTS
  Our data show that Ltbp1L is transcribed coincident with lumen formation, providing a rare marker distinguishing ductal from alveolar luminal lineages. Ltbp1L and Ltbp1S are silent during lactation but robustly induced during involution, peaking at the stage when the remodeling process becomes irreversible. Ltbp1L is also induced within the embryonic mammary mesenchyme and maintained within nipple smooth muscle cells and myofibroblasts. Ltbp1 protein exclusively ensheaths ducts and side branches.
  
  
  CONCLUSIONS
  These data show Ltbp1 is transcriptionally regulated in a dynamic manner that is likely to impose significant spatial restriction on TGFβ bioavailability during mammary development. We hypothesize that Ltbp1 functions in a mechanosensory capacity to establish and maintain ductal luminal cell fate, support and detect ductal distension, trigger irreversible involution, and facilitate nipple sphincter function.
authors.forename: Anupama
authors.initials: A
authors.lastname: Chandramouli
authors.forename: Julia
authors.initials: J
authors.lastname: Simundza
authors.forename: Alicia
authors.initials: A
authors.lastname: Pinderhughes
authors.forename: Minoti
authors.initials: M
authors.lastname: Hiremath
authors.forename: Gustavo
authors.initials: G
authors.lastname: Droguett
authors.forename: David
authors.initials: D
authors.lastname: Frendewey
authors.forename: Pamela
authors.initials: P
authors.lastname: Cowin
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007774:Lactation; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000166:cytology / Q000196:embryology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D053779:Latent TGF-beta Binding Proteins