Estrogen receptor-\u03b1 signaling in post-natal mammary development and breast cancers

Mariam Rusidzé,Elodie Chantalat,Surya Cayre,I Raymond-Letron,Jean-François Arnal,Marine Adlanmérini,Françoise Lenfant,Marie-Ange Deugnier

doi:10.1007/s00018-021-03860-4

Abstract

17β-estradiol controls post-natal mammary gland development and exerts its effects through Estrogen Receptor ERα, a member of the nuclear receptor family. ERα is also critical for breast cancer progression and remains a central therapeutic target for hormone-dependent breast cancers. In this review, we summarize the current understanding of the complex ERα signaling pathways that involve either classical nuclear “genomic” or membrane “non-genomic” actions and regulate in concert with other hormones the different stages of mammary development. We describe the cellular and molecular features of the luminal cell lineage expressing ERα and provide an overview of the transgenic mouse models impacting ERα signaling, highlighting the pivotal role of ERα in mammary gland morphogenesis and function and its implication in the tumorigenic processes. Finally, we describe the main features of the ERα-positive luminal breast cancers and their modeling in mice.

Highlights

The mammary gland is an exocrine gland of ectodermal origin whose primary function is to produce milk for the nourishment of offspring
In humans as in most mammals, mammary morphogenesis is initiated during the embryonic period but the most important part of mammary development and remodeling occurs after birth, throughout puberty, pregnancy, lactation and involution [1–6]
ERα is routinely used as a diagnosis marker supporting the molecular classification of breast cancers [13–15] and remains an essential therapeutic target for hormone-dependent breast cancers, in particular through administration of tamoxifen (TAM) and/ or aromatase inhibitors (AI), that both are very efficient in reducing the risk of cancer recurrence [16–18]

Summary

Introduction

The mammary gland is an exocrine gland of ectodermal origin whose primary function is to produce milk for the nourishment of offspring. The recent development of new transgenic mouse models and omics-based analyses has allowed to better characterize the ERα-positive luminal cell lineage and to further dissect the complex signaling events triggered by estrogens in the mammary epithelium. Estrogens induce the expression of progesterone receptor (PR) and prolactin receptor (PRLR) transcripts, highlighting the pivotal role of ERα signaling in the hormonal response of the developing mammary epithelium [136–138].

Results

Conclusion