Differential expression of genes involved in the epigenetic regulation of cell identity in normal human mammary cell commitment and differentiation

Danila Coradini, Patrizia Boracchi, Saro Oriana, Elia Biganzoli, Federico Ambrogi

Research output: Contribution to journalArticle

Abstract

The establishment and maintenance of mammary epithelial cell identity depends on the activity of a group of proteins, collectively called maintenance proteins, that act as epigenetic regulators of gene transcription through DNA methylation, histone modification, and chromatin remodeling. Increasing evidence indicates that dysregulation of these crucial proteins may disrupt epithelial cell integrity and trigger breast tumor initiation. Therefore, we explored in silico the expression pattern of a panel of 369 genes known to be involved in the establishment and maintenance of epithelial cell identity and mammary gland remodeling in cell subpopulations isolated from normal human mammary tissue and selectively enriched in their content of bipotent progenitors, committed luminal progenitors, and differentiated myoepithelial or differentiated luminal cells. The results indicated that, compared to bipotent cells, differentiated myoepithelial and luminal subpopulations were both characterized by the differential expression of 4 genes involved in cell identity maintenance: CBX6 and PCGF2, encoding proteins belonging to the Polycomb group, and SMARCD3 and SMARCE1, encoding proteins belonging to the Trithorax group. In addition to these common genes, the myoepithelial phenotype was associated with the differential expression of HDAC1, which encodes histone deacetylase 1, whereas the luminal phenotype was associated with the differential expression of SMARCA4 and HAT1, which encode a Trithorax protein and histone acetylase 1, respectively. The luminal compartment was further characterized by the overexpression of ALDH1A3 and GATA3, and the down-regulation of NOTCH4 and CCNB1, with the latter suggesting a block in cell cycle progression at the G2phase. In contrast, myoepithelial differentiation was associated with the overexpression of MYC and the down-regulation of CCNE1, with the latter suggesting a block in cell cycle progression at the G1phase.

Original languageEnglish
Pages (from-to)501-510
Number of pages10
JournalChinese Journal of Cancer
Volume33
Issue number10
DOIs
Publication statusPublished - 2014

    Fingerprint

Keywords

  • Committed luminal progenitors
  • Differentiated myoepithelial/luminal cells
  • Epigenetic regulation
  • Maintenance proteins
  • Mammary epithelial cell identity
  • Normal bipotent cells

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this