ER and PR signaling nodes during mammary gland development
1 Ecole polytechnique fédérale de Lausanne, ISREC - Swiss Institute for Experimental Cancer Research, NCCR Molecular Oncology, SV2832 Station 19, CH-1015 Lausanne, Switzerland
2 Roche Diagnosis GmbH, Oncology, Penzberg, Germany
3 Institute of Oral Biology, Zentrum für Zahnmedizin, Faculty of Medicine, University of Zurich, Zurich, Switzerland
4 Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 Quai Ernest-Ansermet, CH-1211 Genève 4, Switzerland
Breast Cancer Research 2012, 14:210 doi:10.1186/bcr3166Published: 19 July 2012
The ovarian hormones estrogen and progesterone orchestrate postnatal mammary gland development and are implicated in breast cancer. Most of our understanding of the molecular mechanisms of estrogen receptor (ER) and progesterone receptor (PR) signaling stems from in vitro studies with hormone receptor-positive cell lines. They have shown that ER and PR regulate gene transcription either by binding to DNA response elements directly or via other transcription factors and recruiting co-regulators. In addition they cross-talk with other signaling pathways through nongenomic mechanisms. Mouse genetics combined with tissue recombination techniques have provided insights about the action of these two hormones in vivo. It has emerged that hormones act on a subset of mammary epithelial cells and relegate biological functions to paracrine factors. With regards to hormonal signaling in breast carcinomas, global gene expression analyses have led to the identification of gene expression signatures that are characteristic of ERα-positive tumors that have stipulated functional studies of hitherto poorly understood transcription factors. Here, we highlight what has been learned about ER and PR signaling nodes in these different systems and attempt to lay out in which way the insights may converge.