Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics.


Journal Article

Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44(+) progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44(+)p27(+) cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27(+) cells and their proliferation. Our results suggest that pathways controlling p27(+) mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention.

Full Text

Cited Authors

  • Choudhury, S; Almendro, V; Merino, VF; Wu, Z; Maruyama, R; Su, Y; Martins, FC; Fackler, MJ; Bessarabova, M; Kowalczyk, A; Conway, T; Beresford-Smith, B; Macintyre, G; Cheng, Y-K; Lopez-Bujanda, Z; Kaspi, A; Hu, R; Robens, J; Nikolskaya, T; Haakensen, VD; Schnitt, SJ; Argani, P; Ethington, G; Panos, L; Grant, M; Clark, J; Herlihy, W; Lin, SJ; Chew, G; Thompson, EW; Greene-Colozzi, A; Richardson, AL; Rosson, GD; Pike, M; Garber, JE; Nikolsky, Y; Blum, JL; Au, A; Hwang, ES; Tamimi, RM; Michor, F; Haviv, I; Liu, XS; Sukumar, S; Polyak, K

Published Date

  • July 3, 2013

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 117 - 130

PubMed ID

  • 23770079

Pubmed Central ID

  • 23770079

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2013.05.004


  • eng

Conference Location

  • United States