Molecular Profiling of Human Mammary Gland Links Breast Cancer Risk to a p27+ Cell Population with Progenitor Characteristics
Molecular Profiling of Human Mammary Gland Links Breast Cancer Risk to a p27+ Cell Population with Progenitor Characteristics
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DOI：
10.1016/j.stem.2013.05.004
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发表时间：
2013-07-03
期刊：
影响因子：
23.9
通讯作者：
Polyak, Kornelia
中科院分区：
文献类型：
--
作者：
Choudhury, Sibgat;Almendro, Vanessa;Polyak, Kornelia
早期足月妊娠是预防乳腺癌最有效的自然保护措施之一。为了研究这种效应，我们已经表征了来自未经产和经产妇女以及BRCA 1或BRCA 2突变携带者的正常乳腺组织的多种细胞类型的全局基因表达和表观遗传特征。我们发现CD 44（+）祖细胞的显著差异，其中许多干细胞相关基因和途径的水平，包括细胞周期调节因子p27，在没有BRCA 1/BRCA 2突变的经产妇女中较低。我们还注意到经产妇女中CD 44（+）p27（+）细胞的频率显著降低，并使用外植体培养显示，产次相关信号通路在调节p27（+）细胞的数量及其增殖中发挥作用。我们的研究结果表明，控制p27（+）乳腺上皮细胞的途径和这些细胞的数量与乳腺癌的风险有关，可以探索癌症风险评估和预防。
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.