title: Foxa1 is essential for mammary duct formation.
abstract: The transcription factor forkhead box protein A1 (FOXA1) plays a critical role in the proliferation of human breast cancer cells, particularly estrogen receptor alpha (ERα)-positive luminal breast cancer cells. However, genetic studies of the requirement for Foxa1 in mammary tumor formation in mice have been hampered by the lack of a conditional gene ablation. We examined three mouse models of mammary-specific ablation of Foxa1 in ductal epithelial cells to identify the best system for complete and mammary-specific ablation of Foxa1. We found that MMTV-Cre and MMTV-rtTA;Tet-On-Cre led to partial deletion of Foxa1 and attenuated mammary duct formation, whereas Krt14-Cre led to complete ablation of Foxa1 and abolished mammary duct formation, in Foxa1(loxP/loxP) mice. These results demonstrate that Foxa1 is essential for mammary duct formation, and reveal a series of mouse models in which mammary expression of Foxa1 can be attenuated or completely blocked. Our study also suggests a potentially powerful model for complete ablation of Foxa1 in mammary epithelial cells using Krt14-driven Cre expression in an inducible manner, such as Krt14-rtTA;Tet-On-Cre. This model system will facilitate further in vivo functional studies of Foxa1 or other factors in mammary gland development and tumor formation and progression. genesis 54:277-285, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Skerry
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Christelle
authors.initials: C
authors.lastname: Colin-Cassin
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics*; D006801:Humans; D019426:Integrases / Q000235:genetics; D053547:Keratin-14 / Q000235:genetics; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic
chemical_list: C496500:Foxa1 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D053547:Keratin-14; C507446:Krt14 protein, mouse; C045073:Cre recombinase; D019426:Integrases
keywords: Krt14; MMTV; mammary gland; transgenic mice