Effect of Exogenous Epidermal-Like Growth Factors on Mammary Gland Development and Differentiation in the Estrogen Receptor-Alpha Knockout (ERKO) Mouse

  title={Effect of Exogenous Epidermal-Like Growth Factors on Mammary Gland Development and Differentiation in the Estrogen Receptor-Alpha Knockout (ERKO) Mouse},
  author={Nicholas J. Kenney and Arthur Bowman and Kenneth S. Korach and J Carl Barrett and David S Salomon},
  journal={Breast Cancer Research and Treatment},
The development of the mouse mammary gland requires the interaction between several different ovarian and pituitary hormones such as estrogen, progesterone and prolactin as well as several locally-derived growth factors in the mammary gland such as epidermal growth factor (EGF), transforming growth factor α (TGFα), amphiregulin (AR) and heregulin (HRG). The focus of this study was to investigate the degree of mammary growth and differentiation in the adult, virgin mammary gland of wild type (wt… 

Prolactin potentiates transforming growth factor alpha induction of mammary neoplasia in transgenic mice.

It is demonstrated that locally produced Prolactin can strikingly potentiate the carcinogenic actions of another oncogene and modify ovarian hormone responsiveness, suggesting that prolactin signaling may be a potential therapeutic target.

Form and Function: how Estrogen and Progesterone Regulate the Mammary Epithelial Hierarchy

Better understanding of the hierarchal organization of epithelial cell populations in the mammary gland and how the hormonal milieu affects its regulation may provide important insights into the origins of different subtypes of breast cancer.

Roles of epidermal growth factor family in the regulation of postnatal somatic growth.

  • C. Xian
  • Biology
    Endocrine reviews
  • 2007
EGF-R ligands can regulate bone homeostasis by regulating a pool of progenitor cells in the bone marrow through promoting proliferation but suppressing differentiation of bone marrow mesenchymal stem cells.

Roles of EGF Family of Growth Factors in Growth: Overview of Their Roles in Postnatal Growth and Development

EGF-R ligands can regulate bone homeostasis by regulating pool of progenitor cells in the bone marrow through promoting their proliferation but suppressing differentiation of bone marrow mesenchymal stem cells.

Mammary gland development

The knowledge of mammary gland development and mammary stem cell biology has significantly contributed to the understanding of breast cancer and has advanced the discovery of therapies to treat this disease.

The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer

Proper mammary morphogenesis requires the ADAM17-mediated release of AREG from ductal epithelial cells, the subsequent activation of EGFR on stromal cells, and EGFR-dependent stroma responses that in return elicit a new set of epithelial responses, all culminating in the formation of a fully functional ductal tree.

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.

Hormone Signaling Pathways in the Postnatal Mammary Gland

A summary of findings from commonly used cell and animal models, as well as humans, was selected to explain the effects exerted by the main hormones implicated in mammary gland biology.

Modulation of mammary gland development in pre-pubertal mice as affected by soya and milk protein supplements

The mechanism by which α-LA affects glandular development is by modulating the ECM or by promoting the synthesis/activity of EGF, which is known to be oestrogenic and can act on epithelia directly.

Human Breast Progenitor Cell Numbers Are Regulated by WNT and TBX3

Two phenotypically distinguishable lineage-committed progenitor cells that contribute to different structural elements and are regulated via hormonal and non-hormonal mechanisms are identified.



Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis.

The results indicate that an EGF-receptor-mediated pathway remained intact in the mammary gland epithelium in the absence of ovarian steroids and that local availability of either EGF or TGF-alpha is sufficient to stimulate the pattern of normal ductal growth.

Elucidation of a Role for Stromal Steroid Hormone Receptors in Mammary Gland Growth and Development Using Tissue Recombinants

Tissue recombinants in conjunction with steroid receptor deficient mice are used as a tool to dissect the complex paracrine pathways of sex-hormone-regulated epithelial growth and ductal morphogenesis in the mammary gland and other hormone target organs to demonstrate that epithelial steroid receptors are neither necessary nor sufficient for hormonal regulation of epithelial proliferation.

Heregulin induces in vivo proliferation and differentiation of mammary epithelium into secretory lobuloalveoli.

The overall mammary response to growth factors was potentiated by the concomitant presence of E/P, and the in vivo mammary epithelial responses to HRG alpha were more robust than TGF-alpha.

Paracrine mechanisms of mouse mammary ductal growth.

The role of epithelial versus stromal ER in mammary ductal-alveolar growth is reviewed to assess the importance of paracrine mechanisms.

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.

Erbb4 Signaling in the Mammary Gland Is Required for Lobuloalveolar Development and Stat5 Activation during Lactation

It is demonstrated that ErbB4 signaling is necessary for mammary terminal differentiation and Stat5 activation at mid-lactation and that Stat5 was probably inactive when expressed transiently in 293T cells.

Cross-talk between Stat5b and estrogen receptor-alpha and -beta in mammary epithelial cells.

It is demonstrated that estrogen receptor-alpha and -beta are both able to potentiate transcription from a Stat5-responsive promoter when activated by prolactin, and it is concluded that ERalpha and ERbeta act as coactivators for Stat5b through a mechanism which is independent of AF-1 and AF-2.

Persistent changes in gene expression induced by estrogen and progesterone in the rat mammary gland.

Results provide the first support at the molecular level for the hypothesis that hormone-induced persistent changes in gene expression are present in the involuted mammary gland.

Expression of pregnancy-specific genes in preneoplastic mouse mammary tissues from virgin mice.

All major species of casein, alpha, beta, and gamma, were constitutively expressed in these preneoplastic alveolar mammary outgrowths following induction by mouse mammary tumor virus, dimethylbenz(alpha)-anthracene, and/or pituitary isografts.