Amphiregulin: Role in Mammary Gland Development and Breast Cancer

  title={Amphiregulin: Role in Mammary Gland Development and Breast Cancer},
  author={Jean McBryan and Jillian Howlin and Silvia Napoletano and Finian Martin},
  journal={Journal of Mammary Gland Biology and Neoplasia},
Extensive epithelial cell proliferation underlies the ductal morphogenesis of puberty that generates the mammary tree that will eventually fill the fat pad. This estrogen-dependent process is believed to be essentially dependent on locally produced growth factors that act in a paracrine fashion. EGF-like growth factor ligands, acting through EGF receptors are some of the principal promoters of pubertal ductal morphogenesis. Amphiregulin is the most abundant EGF-like growth factor in the… 
Amphiregulin mediates progesterone-induced mammary ductal development during puberty
A novel P-specific effect through AREG is demonstrated to cause EB formation and proliferation in the developing mammary gland both before and during puberty, demonstrating the potential to affect breast cancer risk associated with pubertal mammaries development.
FOXA1 is an essential determinant of ERα expression and mammary ductal morphogenesis
Foxa1 deficiency causes a defect in hormone-induced mammary ductal invasion associated with a loss of terminal end bud formation and ERα expression, revealing that FOXA1 is necessary for hormonal responsiveness in the developing mammary gland and ER α-positive breast cancers, at least in part, through its control of ER α expression.
Atbf1 Regulates Pubertal Mammary Gland Development Likely by Inhibiting the Pro-Proliferative Function of Estrogen-ER Signaling
Findings indicate that Atbf1 plays a role in the development of pubertal mammary gland likely by modulating the function of estrogen-ER signaling in luminal cells and by modifying gene expression in basal cells.
GPER Mediates Estrogen-Induced Signaling and Proliferation in Human Breast Epithelial Cells and Normal and Malignant Breast
This is the first study to demonstrate GPER-dependent proliferation in primary normal and malignant human tissue, revealing a role for GPER in estrogen-induced breast physiology and pathology.
Progression of Hormone-Dependent Mammary Tumors After Dormancy: Role of Wnt Pathway
It is believed that the cluster of co-regulated genes in basal human breast cancer and mouse mammary tumors resuming growth after dormancy might be mechanistically associated to the activation of Wnt pathway, which might induce proliferation from mammary progenitor basal cells.
Epiregulin contributes to breast tumorigenesis through regulating matrix metalloproteinase 1 and promoting cell survival
BackgroundThe epidermal growth factor (EGF) family of ligands has been implicated in promoting breast cancer initiation, growth and progression. The contributions of EGF family ligands and their
Estrogen receptor-α signaling in post-natal mammary development and breast cancers
The cellular and molecular features of the luminal cell lineage expressing ERα are described and an overview of the transgenic mouse models impacting ERα signaling is provided, highlighting the pivotal role of ERα in mammary gland morphogenesis and function and its implication in the tumorigenic processes.
The multiple roles of amphiregulin in human cancer.
Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells.
The data show a novel interplay between PRL and E(2) to modulate gene regulation in breast cancer cells, synergised to regulate EGR3, while multiple genes were regulated additively.
Amphiregulin regulates proliferation and migration of HER2-positive breast cancer cells
It is concluded that AREG is involved in regulating the proliferation and migration of erbB2/HER2-positive breast cancer cells.


Amphiregulin is an essential mediator of estrogen receptor α function in mammary gland development
It is shown that amphiregulin is the unique EGF family member to be transcriptionally induced by estrogen in the mammary glands of puberal mice at a time of exponential expansion of the ductal system.
Induction of ductal morphogenesis and lobular hyperplasia by amphiregulin in the mouse mammary gland.
This is the first study to demonstrate that AR can reestablish the early developmental activity of ductal mammary epithelium and induce hyperplasia in vivo and suggest that AR may be an important intermediary in glandular maturation and early malignant progression.
The role of amphiregulin in breast cancer
SummaryAmphiregulin (AR) is an epidermal growth factor (EGF)-related peptide that operates exclusively through the EGF receptor and that can bind to heparin. AR also possesses nuclear localization
Amphiregulin-EGFR signaling regulates PTHrP gene expression in breast cancer cells
It appears that autocrine stimulation of EGFR signaling by amphiregulin is coupled to PTHrP gene expression via EGFR Tyr992 and MAPK, and that this pathway may contribute to P THrP expression by breast tumor cells.
ErbB2 is required for ductal morphogenesis of the mammary gland.
The functions of ErbB2 during normal mouse mammary gland development are investigated, and the results may have implications for the aggressive phenotypes associated with ERBB2-overexpressing mammary carcinomas.
Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin
ADAM17 plays a crucial role in mammary morphogenesis by releasing AREG from mammary epithelial cells, thereby eliciting paracrine activation of stromal EGFR and reciprocal responses that regulate mammary encapsulated epithelial development.
Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development.
New insights are gained into the nature of stromal-epithelial interactions in the mammary gland, and how they regulate ductal growth and branching morphogenesis through the use of tissue recombinants and transplantation.
Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth
It is demonstrated that the mammary-specific ablation of erbB2 through Cre-mediated recombination leads to a striking ductal elongation defect, which indicates that erb B2 plays a critical role in the initial stages of mammary gland morphogenesis.
Paracrine signaling through the epithelial estrogen receptor α is required for proliferation and morphogenesis in the mammary gland
It is shown that mammary glands reconstituted with ERα−/− mammary epithelium exposed to pregnancy hormones show increased transcription of milk protein genes, indicating that ERα signaling is not an absolute requirement for a transcriptional response toregnancy hormones.
Preneoplastic mammary tumor markers: Cripto and amphiregulin are overexpressed in hyperplastic stages of tumor progression in transgenic mice
Amphiregulin (Ar) and Cripto (Cr) are autocrine growth factors for mammary cells and both should have potential value as markers of preneoplastic change in mammary tissue.