Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/5967
Title: Progesterone and Wnt4 control mammary stem cells via myoepithelial crosstalk
Authors: Rajaram, Renuga Devi
Buric, Duje
Caikovski, Marian
Ayyanan, Ayyakkannu
Rougemont, Jacques
Shan, Jingdong
Vainio, Seppo J.
Yalçın Özuysal, Özden
Brisken, Cathrin
Yalçın Özuysal, Özden
Keywords: Canonical Wnt signaling
Hormones
Mammary stem cells
Myoepithelium
Paracrine
Wnt4 protein
Issue Date: 4-Mar-2015
Publisher: John Wiley and Sons Inc.
Source: Rajaram, R.D., Buric, D., Caikovski, M., Ayyanan, A., Rougemont, J., Shan, J., Vainio, S.J., Yalçın Özuysal, Ö., and Brisken, C. (2015). Progesterone and Wnt4 control mammary stem cells via myoepithelial crosstalk. EMBO Journal, 34(5), 641-652. doi:10.15252/embj.201490434
Abstract: Ovarian hormones increase breast cancer risk by poorly understood mechanisms. We assess the role of progesterone on global stem cell function by serially transplanting mouse mammary epithelia. Progesterone receptor (PR) deletion severely reduces the regeneration capacity of the mammary epithelium. The PR target, receptor activator of Nf-κB ligand (RANKL), is not required for this function, and the deletion of Wnt4 reduces the mammary regeneration capacity even more than PR ablation. A fluorescent reporter reveals so far undetected perinatal Wnt4 expression that is independent of hormone signaling. Pubertal and adult Wnt4 expression is specific to PR+ luminal cells and requires intact PR signaling. Conditional deletion of Wnt4 reveals that this early, previously unappreciated, Wnt4 expression is functionally important. We provide genetic evidence that canonical Wnt signaling in the myoepithelium required PR and Wnt4, whereas the canonical Wnt signaling activities observed in the embryonic mammary bud and in the stroma around terminal end buds are independent of Wnt4. Thus, progesterone and Wnt4 control stem cell function through a luminal-myoepithelial crosstalk with Wnt4 acting independent of PR perinatally. Synopsis This paper ascribes a new role for Wnt4 in pre-pubertal mammary gland development while revealing luminal cells to respond to Wnt activation. During regeneration, Wnt4 interacts with progesterone receptor signaling, correcting previous notions on RANKL signaling in this context. Wnt4 is an essential control factor for mammary epithelial stem cell function. RANKL is not required for mammary gland regeneration potential. Wnt4 activates canonical Wnt signaling in the basal/myoepithelial compartment. Progesterone receptor signaling is required for mammary epithelial Wnt4 expression already during puberty. This paper ascribes a new role for Wnt4 in pre-pubertal mammary gland development while revealing luminal cells to respond to Wnt activation. During regeneration, Wnt4 interacts with progesterone receptor signaling, correcting previous notions on RANKL signaling in this context.
URI: https://doi.org/10.15252/embj.201490434
http://hdl.handle.net/11147/5967
ISSN: 0261-4189
0261-4189
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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