TY - JOUR
T1 - Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics
AU - Choudhury, Sibgat
AU - Almendro, Vanessa
AU - Merino, Vanessa F.
AU - Wu, Zhenhua
AU - Maruyama, Reo
AU - Su, Ying
AU - Martins, Filipe C.
AU - Jo Fackler, Mary
AU - Bessarabova, Marina
AU - Kowalczyk, Adam
AU - Conway, Thomas
AU - Beresford-Smith, Bryan
AU - Macintyre, Geoff
AU - Cheng, Yu Kang
AU - Lopez-Bujanda, Zoila
AU - Kaspi, Anthony
AU - Hu, Rong
AU - Robens, Judith
AU - Nikolskaya, Tatiana
AU - Haakensen, Vilde D.
PY - 2013/7/3
Y1 - 2013/7/3
N2 - 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. 2013
AB - 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. 2013
UR - http://www.scopus.com/inward/record.url?scp=84893192283&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2013.05.004
DO - 10.1016/j.stem.2013.05.004
M3 - Article
C2 - 23770079
AN - SCOPUS:84893192283
SN - 1934-5909
VL - 13
SP - 117
EP - 130
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -
