ID4 controls luminal lineage commitment in normal mammary epithelium and inhibits BRCA1 function in basal-like breast cancer

Endocr Relat Cancer. 2016 Sep;23(9):R381-92. doi: 10.1530/ERC-16-0196. Epub 2016 Jul 13.

Abstract

Inhibitor of differentiation (ID) proteins are key regulators of development and tumorigenesis. One member of this family, ID4, controls lineage commitment during mammary gland development by acting upstream of key developmental pathways. Recent evidence suggests an emerging role for ID4 as a lineage-dependent proto-oncogene that is overexpressed and amplified in a subset of basal-like breast cancers (BLBCs), conferring poor prognosis. Several lines of evidence suggest ID4 may suppress BRCA1 function in BLBC and in doing so, define a subset of BLBC patients who may respond to therapies traditionally used in BRCA1-mutant cancers. This review highlights recent advances in our understanding of the requirement for ID4 in mammary lineage commitment and the role for ID4 in BLBC. We address current shortfalls in this field and identify important areas of future research.

Keywords: BRCA1; ID4; basal-like breast cancer; inhibitor of differentiation 4; lineage dependent oncogene.

Publication types

  • Review

MeSH terms

  • Animals
  • BRCA1 Protein / metabolism*
  • Breast / metabolism*
  • Breast Neoplasms / metabolism*
  • Epithelium / metabolism*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Humans
  • Inhibitor of Differentiation Proteins / metabolism*
  • Oncogenes
  • Proto-Oncogene Mas

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Estrogen Receptor alpha
  • ID4 protein, human
  • Inhibitor of Differentiation Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas