1. Dachshund Depletion Disrupts Mammary Gland Development and Diverts the Composition of the Mammary Gland Progenitor Pool.
- Author
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Jiao X, Li Z, Wang M, Katiyar S, Di Sante G, Farshchian M, South AP, Cocola C, Colombo D, Reinbold R, Zucchi I, Wu K, Tabas I, Spike BT, and Pestell RG
- Subjects
- 3T3 Cells, Animals, Cells, Cultured, Eye Proteins metabolism, Female, GATA3 Transcription Factor genetics, GATA3 Transcription Factor metabolism, GTP-Binding Proteins genetics, GTP-Binding Proteins metabolism, Keratin-5 genetics, Keratin-5 metabolism, Mammary Glands, Animal cytology, Mammary Glands, Animal metabolism, Mice, Mouse Embryonic Stem Cells cytology, Rats, Receptor, Notch1 genetics, Receptor, Notch1 metabolism, Smad Proteins genetics, Smad Proteins metabolism, Transforming Growth Factor beta metabolism, Eye Proteins genetics, Mammary Glands, Animal growth & development, Mouse Embryonic Stem Cells metabolism
- Abstract
DACH1 abundance is reduced in human malignancies, including breast cancer. Herein DACH1 was detected among multipotent fetal mammary stem cells in the embryo, among mixed lineage precursors, and in adult basal cells and (ERα
+ ) luminal progenitors. Dach1 gene deletion at 6 weeks in transgenic mice reduced ductal branching, reduced the proportion of mammary basal cells (Lin- CD24med CD29high ) and reduced abundance of basal cytokeratin 5, whereas DACH1 overexpression induced ductal branching, increased Gata3 and Notch1, and expanded mammosphere formation in LA-7 breast cells. Mammary gland-transforming growth factor β (TGF-β) activity, known to reduce ductal branching and to reduce the basal cell population, increased upon Dach1 deletion, associated with increased SMAD phosphorylation. Association of the scaffold protein Smad anchor for receptor activation with Smad2/3, which facilitates TGF-β activation, was reduced by endogenous DACH1. DACH1 increases basal cells, enhances ductal formation and restrains TGF-β activity in vivo., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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