Foxa1 is essential for mammary duct formation

Yi Liu, Yongbing Zhao, Benjamin Skerry, Xiao Wang, Christelle Colin-Cassin, Derek C Radisky, Klaus H. Kaestner, Zhaoyu Li

Research output: Contribution to journalArticle

5 Scopus citations

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 Foxa1loxP/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.

Original languageEnglish (US)
JournalGenesis
DOIs
StateAccepted/In press - 2016

Keywords

  • Krt14
  • Mammary gland
  • MMTV
  • Transgenic mice

ASJC Scopus subject areas

  • Endocrinology
  • Cell Biology
  • Genetics

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    Liu, Y., Zhao, Y., Skerry, B., Wang, X., Colin-Cassin, C., Radisky, D. C., Kaestner, K. H., & Li, Z. (Accepted/In press). Foxa1 is essential for mammary duct formation. Genesis. https://doi.org/10.1002/dvg.22929