@article{c3f3733536f74f15afe4c23ffb5872e7,
title = "Dachshund Depletion Disrupts Mammary Gland Development and Diverts the Composition of the Mammary Gland Progenitor Pool",
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.",
keywords = "breast cancer, DACH, mammary gland, SARA, stem cells, TGF-β",
author = "Xuanmao Jiao and Zhiping Li and Min Wang and Sanjay Katiyar and \{Di Sante\}, Gabriele and Mehdi Farshchian and South, \{Andrew P.\} and Cinzia Cocola and Daniele Colombo and Rolland Reinbold and Ileana Zucchi and Kongming Wu and Ira Tabas and Spike, \{Benjamin T.\} and Pestell, \{Richard G.\}",
note = "Funding Information: This work was supported in part by R01CA132115, (to R.G.P.), a generous grant from the Dr. Ralph and Marian Falk Medical Research Trust (to R.G.P.), a grant from the Breast Cancer Research Foundation. The Department disclaims responsibility for any analysis, interpretations, or conclusions. R.G.P. holds ownership interests in, and serves as CSO/Founder of the biopharmaceutical companies ProstaGene and LightSeed, and is CMO of CytoDyn. R.G.P. holds ownership interests (value unknown) in several issued and submitted patent applications. This work was also supported by the CNR-Flag Projects Epigen and Interomics (to I.Z.). M.F. is supported by the Sigrid Jus{\'e}lius Foundation, Orion Research Foundation, and the Finnish Society of Dermatology. K.W. is supported by the National Natural Science Foundation of China no. 81572608 and no. 81874120. Funding Information: This work was supported in part by R01CA132115, (to R.G.P.), a generous grant from the Dr. Ralph and Marian Falk Medical Research Trust (to R.G.P.), a grant from the Breast Cancer Research Foundation . The Department disclaims responsibility for any analysis, interpretations, or conclusions. R.G.P. holds ownership interests in, and serves as CSO/Founder of the biopharmaceutical companies ProstaGene and LightSeed, and is CMO of CytoDyn. R.G.P. holds ownership interests (value unknown) in several issued and submitted patent applications. This work was also supported by the CNR -Flag Projects Epigen and Interomics (to I.Z.). M.F. is supported by the Sigrid Jus{\'e}lius Foundation , Orion Research Foundation , and the Finnish Society of Dermatology . K.W. is supported by the National Natural Science Foundation of China no. 81572608 and no. 81874120 . Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2019",
month = jan,
day = "8",
doi = "10.1016/j.stemcr.2018.11.010",
language = "English",
volume = "12",
pages = "135--151",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "1",
}
