Hormone Action in the Mammary Gland

Abstract

A woman's breast cancer risk is affected by her reproductive history. The hormonal milieu also influences the course of the disease. The female reproductive hormones, estrogens, progesterone, and prolactin, have a major impact on breast cancer and control postnatal mammary gland development. Analysis of hormone receptor mutant mouse strains combined with tissue recombination techniques and proteomics revealed that sequential activation of hormone signaling in the mammary epithelium is required for progression of morphogenesis. Hormones impinge on a subset of luminal mammary epithelial cells (MECs) that express hormone receptors and act as sensor cells translating and amplifying systemic signals into local stimuli. Proliferation is induced by paracrine mechanisms mediated by distinct factors at different stages. Tissue and stage specificity of hormonal signaling is achieved at the molecular level by different chromatin contexts and differential recruitment of coactivators and corepressors.

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…Female reproductive hormones such as E2 and progesterone are key regulators of postnatal development of the mammary gland as determined by endocrine disruption and replacement studies in rodents [27]. The mammary gland is underdeveloped at birth; however, E2 and progesterone initiate maturation of the mammary gland at the onset of puberty [3,28]. In particular, E2 triggers ductal elongation during puberty [29,30].…”

“…The levels of estrogen in blood and tissue are associated with breast cancer carcinogenesis [2]. Estrogen signaling is a key regulator of postnatal development of mam-mary gland, breast carcinogenesis, and progression when estrogen signaling pathways become dysregulated [3]. Thus far, estrogen receptor signaling is the most attractive target for clinical therapy of ER-positive breast cancer.…”

“…Thus far, estrogen receptor signaling is the most attractive target for clinical therapy of ER-positive breast cancer. Estrogen receptors (ERs) are liganddependent transcription factors that regulate genes that are involved in cell proliferation, differentiation, apoptosis, and cell migration [3]. Dysregulated estrogen receptor signaling is tightly associated with breast tumor initiation and invasion [4].…”

Progesterone Stimulates Proliferation and Promotes Cytoplasmic Localization of the Cell Cycle Inhibitor p27 in Steroid Receptor Positive Breast Cancers

“…Because ovariectomy completely blocks development of carcinogen-induced tumors and P alone does not support mammary cancer development in ovariectomized rats [32], we conclude that E is a critical factor for tumor initiation and development. In general, the presence of E is permissive for P action in vivo because E signaling stimulates PR expression and, thus, allows robust P action [33]. However, the majority of lesions in E-treated rats were DCIS or noninvasive carcinomas.…”

Progesterone signalling in breast cancer: a neglected hormone coming into the limelight

“…3) showed that epithelial ERα signalling 41 and epithelial PR 42 signalling are required at subsequent stages of mammary gland development (reviewed in REF. 43). Indeed, in the absence of epithelial PR signalling in an otherwise PR-intact adult mouse, cell proliferation in the mammary epithelium is minimal 35 .…”