Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics.
Cell Stem Cell
; 13(1): 117-30, 2013 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-23770079
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Paridade
/
Células-Tronco
/
Neoplasias da Mama
/
Linhagem da Célula
/
Perfilação da Expressão Gênica
/
Glândulas Mamárias Humanas
/
Inibidor de Quinase Dependente de Ciclina p27
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos