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

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Cell stem cell

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      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.

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      Author and article information

      Affiliations
      [1 ] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
      Journal
      Cell Stem Cell
      Cell stem cell
      1875-9777
      1875-9777
      Jul 3 2013
      : 13
      : 1
      S1934-5909(13)00197-5
      10.1016/j.stem.2013.05.004
      23770079
      3703476
      NIHMS482224
      Copyright © 2013 Elsevier Inc. All rights reserved.

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