posters International Association for Breast Cancer Research 2014

Inhibitor of Differentiation 4 (ID4) maintains mammary stem cell homeostasis and identifies a subset of poor-prognosis basal-like breast cancers with a stem-like phenotype (#109)

Simon Junankar 1 , Laura Baker 1 , Daniel Roden 1 , Sandra O'Toole 1 2 , Sunil Lakhani 3 4 , Peter Simpson 3 4 , Matthew Naylor 5 , Christopher Ormandy 1 , Alexander Swarbrick 1
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  3. UQ Centre for Clinical Research, School of Medicine , The University of Queensland, Brisbane, Qld, Australia
  4. Pathology Queensland, The Royal Brisbane and Women’s Hospital, Herston, Qld, Australia
  5. Discipline of Physiology and Bosch Institute, School of Medical Sciences , University of Sydney, Sydney, NSW, Australia

Basal-like breast cancers (BLBC) are heterogenous, poorly differentiated and present with limited therapeutic opportunities. We investigated the role of the HLH transcription factor ID4 in breast stem cells and BLBC aetiology. Id4 defines a subset of Cd24+Cd29hi basal mammary epithelial cells enriched for stem/progenitor cell gene expression and mammary repopulating capacity. Id4 is required for mammary ductal morphogenesis in vivo and epithelial cell proliferation in vitro. Id4 overexpression maintains the stem/progenitor cell pool by restricting luminal differentiation, mediated via suppression of BrCa1 and the Notch-Elf5 axis. ID4 is highly expressed by approximately half of all BLBCs, which possess a transcriptional signature resembling mammary stem cells. ID4-positive BLBCs have a very poor prognosis across multiple clinical cohorts. This study identifies ID4 as a key regulator of mammary stem/progenitors and identifies a subset of BLBCs with poor prognosis and a basal cell-like phenotype.