Molecular Profiling of Human Mammary Gland Links Breast Cancer Risk to a p27+ Cell Population with Progenitor Characteristics
Menée sur des cellules de tissu normal du sein, cette étude montre que des cellules surexprimant p27 sont associées à un risque de cancer du sein, ce qui permet de rendre compte de l'effet protecteur d'une grossesse précoce sur la réduction de ce risque
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. "Parity-related molecular alterations in control but not BRCA1/BRCA2 normal breast "Stem cell-related pathways are decreased in cells from parous women "Number of p27+ cells with progenitor features relates to breast cancer risk "p27 and TGF-² signaling are key regulators of mammary epithelial progenitors Profiling of cell populations from the human mammary gland provides hints about differences in progenitors that may underlie the protective effect that early pregnancy has in reducing the risk for breast cancer.
http://linkinghub.elsevier.com/retrieve/pii/S1934590913001975