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首页> 外文期刊>Endocrinology >DNA replication licensing and progenitor numbers are increased by progesterone in normal human breast.
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DNA replication licensing and progenitor numbers are increased by progesterone in normal human breast.

机译：孕酮在正常人的乳房中会增加DNA复制许可和祖细胞数量。

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Proliferation in the nonpregnant human breast is highest in the luteal phase of the menstrual cycle when serum progesterone levels are high, and exposure to progesterone analogues in hormone replacement therapy is known to elevate breast cancer risk, yet the proliferative effects of progesterone in the human breast are poorly understood. In a model of normal human breast, we have shown that progesterone increased incorporation of 5-bromo-2'-deoxyuridine and increased cell numbers by activation of pathways involved in DNA replication licensing, including E2F transcription factors, chromatin licensing and DNA replication factor 1 (Cdt1), and the minichromosome maintenance proteins and by increased expression of proteins involved in kinetochore formation including Ras-related nuclear protein (Ran) and regulation of chromosome condensation 1 (RCC1). Progenitor cells competent to give rise to both myoepithelial and luminal epithelial cells were increased by progesterone, showing that progesterone influences epithelial cell lineage differentiation. Therefore, we have demonstrated that progesterone augments proliferation of normal human breast cells by both activating DNA replication licensing and kinetochore formation and increasing bipotent progenitor numbers.
机译：当血清孕酮水平高时，未怀孕的人乳房中的增殖在月经的黄体期最高，已知激素替代疗法中接触孕酮类似物会增加患乳腺癌的风险，但孕酮在人乳房中的增殖作用知之甚少。在正常人的乳房模型中，我们已经显示，孕酮通过激活涉及DNA复制许可的途径（包括E2F转录因子，染色质许可和DNA复制因子1）而增加了5-bromo-2'-deoxyuridine的掺入并增加了细胞数量。 （Cdt1）和微染色体维持蛋白，以及通过增加与动粒形成有关的蛋白的表达，包括与Ras相关的核蛋白（Ran）和染色体浓缩1（RCC1）的调控。孕酮可同时激活肌上皮和管腔上皮细胞，而祖细胞增加，表明孕酮影响上皮细胞谱系分化。因此，我们已经证明，孕酮通过激活DNA复制许可和动粒形成以及增加双能祖细胞数量来增加正常人乳腺细胞的增殖。

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