Sibgat Choudhury 1 , Vanessa Almendro , Vanessa F Merino , Zhenhua Wu , Reo Maruyama , Ying Su , Filipe C Martins , Mary Jo Fackler , Marina Bessarabova , Adam Kowalczyk , Thomas Conway , Bryan Beresford-Smith , Geoff Macintyre , Yu-Kang Cheng , Zoila Lopez-Bujanda , Antony Kaspi , Rong Hu , Judith Robens , Tatiana Nikolskaya , Vilde D Haakensen , Stuart J Schnitt , Pedram Argani , Gabrielle Ethington , Laura Panos , Michael Grant , Jason Clark , William Herlihy , S Joyce Lin , Grace Chew , Erik W Thompson , April Greene-Colozzi , Andrea L Richardson , Gedge D Rosson , Malcolm Pike , Judy E Garber , Yuri Nikolsky , Joanne L Blum , Alfred Au , E Shelley Hwang , Rulla M Tamimi , Franziska Michor , Izhak Haviv , X Shirley Liu , Saraswati Sukumar , Kornelia Polyak
Jul 3 2013
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.