Inhibition of lobuloalveolar development by FOXC1 overexpression in the mouse mammary gland

Scientific Reports
Bowen GaoX Cui

Abstract

The forkhead box transcription factor FOXC1 plays a critical role in embryogenesis and the development of many organs. Its mutations and high expression are associated with many human diseases including breast cancer. Although FOXC1 knockout mouse studies showed that it is not required for mammary gland development during puberty, it is not clear whether its overexpression alters normal mammary development in vivo. To address this question, we generated transgenic mice with mammary-specific FOXC1 overexpression. We report that transgenic FOXC1 overexpression suppresses lobuloalveologenesis and lactation in mice. This phenotype is associated with higher percentages of estrogen receptor-, progesterone receptor-, or ki67-positive mammary epithelial cells in the transgenic mice at the lactation stage. We also show that expression of the Elf5 transcription factor, a master regulator of mammary alveologenesis and luminal cell differentiation, is markedly reduced in mammary epithelial cells of transgenic mice. Likewise, levels of activated Stat5, another inducer of alveolar expansion and a known mediator of the Elf5 effect, are also lowered in those cells. In contrast, the cytokeratin 8-positive mammary cell population with progenitor...Continue Reading

References

Jul 1, 1990·Statistics in Medicine·Y Hochberg, Y Benjamini
Mar 19, 2002·The Journal of Steroid Biochemistry and Molecular Biology·G ShyamalaS Nandi
Sep 15, 2004·Toxicology and Applied Pharmacology·Jonathan M Shipley, David J Waxman
Oct 19, 2005·Nature Reviews. Molecular Cell Biology·Lothar Hennighausen, Gertraud W Robinson
Sep 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yuxin FengSohaib A Khan
Oct 19, 2007·Nature Reviews. Cancer·Stephen S Myatt, Eric W-F Lam
Feb 26, 2008·Development·Christine J Watson, Walid T Khaled
Mar 5, 2008·Genes & Development·Samantha R OakesChristopher J Ormandy
Mar 19, 2008·Genes & Development·Lothar Hennighausen, Gertraud W Robinson
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jan 31, 2009·The American Journal of Pathology·Lisa M ArendtLinda A Schuler
Apr 30, 2009·The Journal of Endocrinology·Josephine F TrottRussell C Hovey
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Joseph H TaubeSendurai A Mani
Jan 15, 2011·Source Code for Biology and Medicine·Guorong XuDongxiao Zhu
Dec 24, 2011·Molecular and Cellular Endocrinology·Alison E Obr, Dean P Edwards
Apr 24, 2012·Stem Cells·Rumela ChakrabartiSatrajit Sinha
Jul 31, 2012·Wiley Interdisciplinary Reviews. Developmental Biology·Hector Macias, Lindsay Hinck
Aug 23, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Limin XiaKaichun Wu
Jun 26, 2013·Nature Reviews. Cancer·Eric W-F LamChuay-Yeng Koo
Dec 17, 2014·ELife·Parthiv HaldipurKathleen J Millen
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jun 5, 2015·Journal of the National Cancer Institute·Tor W JensenPartha S Ray

❮ Previous
Next ❯

Citations

Feb 16, 2019·Cancers·L Niall Gilding, Tim C P Somervaille

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE104443

Methods Mentioned

BETA
transgenic
immunoprecipitation
pull down
RNA-Seq
PCR
biopsies
Genotyping
Protein Assay
ChIP
pull-down

Software Mentioned

Tophat2
DAVID
Bcl2fastq2
Illumina
SAMMate
Ensembl

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.