Ltbp1Lis focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution
Ltbp1Lis focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution
Abstract Introduction 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.
- New York University School of Medicine United States
- New York University School of Medicine
- Regeneron (United States) United States
- New York University United States
Medicine(all), Gene Expression Regulation, Developmental, Muscle, Smooth, Mice, Mutant Strains, Up-Regulation, Mesoderm, Mice, Inbred C57BL, Mammary Glands, Animal, Latent TGF-beta Binding Proteins, Cell Movement, Pregnancy, Animals, Lactation, Cell Lineage, Female, Promoter Regions, Genetic, Research Article
Medicine(all), Gene Expression Regulation, Developmental, Muscle, Smooth, Mice, Mutant Strains, Up-Regulation, Mesoderm, Mice, Inbred C57BL, Mammary Glands, Animal, Latent TGF-beta Binding Proteins, Cell Movement, Pregnancy, Animals, Lactation, Cell Lineage, Female, Promoter Regions, Genetic, Research Article
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