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Estrogen receptor beta is a negative regulator of mammary cell proliferation.

机译：雌激素受体β是乳腺细胞增殖的负调节剂。

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摘要

The mammary gland cell growth and differentiation are under the control of both systemic hormones and locally produced growth factors. Among all these important hormones and growth factors, estrogen plays a central role in mammary gland development. The biological function of estrogen is mediated by estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). Both ERalpha and ERbeta are expressed in the mammary gland, but with distinct expression patterns. In the mammary gland, ERalpha has been proved to be the estrogen receptor that mediates the mitogenic function of estrogen. However the function of ERbeta in mammary cell proliferation is less understood and there remains some controversy. Accumulating evidence indicates that ERbeta, unlike ERalpha, is a negative regulator of mammary epithelial cell proliferation.;In this dissertation, ERalpha and ERbeta were evaluated for their expression patterns in the mammary gland. In the proestrus phase, ERalpha was detected in about 20% of mammary epithelial cells; in the diestrus phase, no ERalpha staining was detected in the mammary gland. ERbeta was expressed in more than 50% of mammary epithelial cells and ERbeta staining was detected in some stromal cells in the proestrus phase. In the diestrus phase, ERbeta staining cells were very limited and the staining intensity was very weak. These data suggest that the expression levels of both ERalpha and ERbeta undergo dynamic changes during the estrous cycle. In the ovariectomised (OVX) rats, both ERalpha and ERbeta were detected in more than 50% of mammary epithelial cells. Compared with the ovary-intact rats, the mammary gland of the OVX rats showed more cells with ERalpha expression, but the staining intensity was weaker. Taken together, the expression of ERalpha and ERbeta is regulated by estrogen in normal mammary gland, while without estrogen stimulation in the OVX rats, more mammary cells showed ERalpha expression, but at a lower level in these cells.;The effects of ERalpha and ERbeta on mammary cell proliferation were studied by two different approaches, activation of endogenous ERalpha and ERbeta via selective agonists, and overexpression of ERalpha and ERbeta via lentiviral infection. In the first approach, we used ERalpha and ERbeta selective agonists, propylpyrazole-triol (PPT) and diarylpropionitrile (DPN) respectively, to activate endogenous ERalpha and ERbeta in the OVX rats. We found that ERbeta selective agonist DPN counteracts the proliferative effect of ERalpha selective agonist PPT in the mammary gland. In the second approach, ERalpha and ERbeta were ectopically overexpressed in the mammary gland of mature virgin rats by lentivirus infection. We found that ERbeta overexpression significantly decreased mammary cell proliferation rate in both the proestrus and diestrus phases, indicating that ERbeta, unlike ERalpha, is a negative regulator for mammary cell proliferation. Collectively, these data supports that in contrast to ERalpha, ERbeta activation or overexpression is able to inhibit mammary cell proliferation.
机译：乳腺细胞的生长和分化受全身激素和局部产生的生长因子的控制。在所有这些重要的激素和生长因子中，雌激素在乳腺发育中起着核心作用。雌激素的生物学功能由雌激素受体α（ERalpha）和雌激素受体β（ERbeta）介导。 ERalpha和ERbeta均在乳腺中表达，但表达模式不同。在乳腺中，ERalpha已被证明是介导雌激素促有丝分裂功能的雌激素受体。然而，ERbeta在乳腺细胞增殖中的功能尚不为人所知，并且仍然存在一些争议。越来越多的证据表明，ERbeta与ERalpha不同，它是乳腺上皮细胞增殖的负调节剂。本文对ERalpha和ERbeta在乳腺中的表达模式进行了评估。在发情期，在大约20％的乳腺上皮细胞中检测到ERalpha。在二头肌阶段，在乳腺中未检测到ERalpha染色。 ERbeta在超过50％的乳腺上皮细胞中表达，并且在发情期的某些基质细胞中检测到ERbeta染色。在二期阶段，ERbeta染色细胞非常有限，染色强度非常弱。这些数据表明，在发情周期中，ERalpha和ERbeta的表达水平都会发生动态变化。在卵巢切除（OVX）大鼠中，超过50％的乳腺上皮细胞中都检测到ERalpha和ERbeta。与卵巢完整的大鼠相比，OVX大鼠的乳腺显示出更多具有ERalpha表达的细胞，但染色强度较弱。两者合计，ERalpha和ERbeta的表达受正常乳腺中的雌激素调节，而在没有雌激素刺激的OVX大鼠中，更多的乳腺细胞显示ERalpha的表达，但在这些细胞中的表达水平较低； ERalpha和ERbeta的作用通过两种不同的方法研究了对哺乳动物细胞增殖的影响：通过选择性激动剂激活内源性ERalpha和ERbeta，以及通过慢病毒感染过度表达ERalpha和ERbeta。在第一种方法中，我们分别使用ERalpha和ERbeta选择性激动剂，丙基吡唑三醇（PPT）和二芳基丙腈（DPN）激活OVX大鼠的内源性ERalpha和ERbeta。我们发现ERbeta选择性激动剂DPN抵消了ERalpha选择性激动剂PPT在乳腺中的增殖作用。在第二种方法中，慢病毒感染使ERalpha和ERbeta在成熟的处女大鼠的乳腺中异位过表达。我们发现ERbeta的过表达显着降低了前期和雌激素期的乳腺细胞增殖速率，表明ERbeta与ERalpha不同，它是乳腺细胞增殖的负调节剂。总体而言，这些数据支持与ERalpha相比，ERbeta激活或过表达能够抑制乳腺细胞增殖。

著录项

  • 作者

    Song, Xiaozheng.;

  • 作者单位

    The University of Vermont and State Agricultural College.;

  • 授予单位 The University of Vermont and State Agricultural College.;
  • 学科 Animal sciences.;Molecular biology.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 251 p.
  • 总页数 251
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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