Pattern of distribution of cells positive for estrogen receptor α and progesterone receptor in relation to proliferating cells in the mammary gland

Pattern of distribution of cells positive for estrogen receptor α and progesterone receptor in relation to proliferating cells in the mammary gland
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DOI:
10.1023/a:1006186719322
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发表时间:
1999-02-01
影响因子:
3.8
通讯作者:
Russo, IH
Russo, IH
中科院分区:
医学2区
文献类型:
--
作者:
Russo, J;Ao, X;Russo, IH

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由于乳腺的生长发育离不开细胞的增殖,而雌激素被认为在促进细胞增殖中起主要作用,而黄体酮则影响其分化,因此本研究旨在验证正常乳腺中含有类固醇激素受体的细胞与增殖细胞之间的关系。对12例乳腺样品进行1型小叶(Lob1)、Lob2、Lob3和Lob4的含量分析,并采用特异性抗体双免疫细胞化学技术检测含有雌激素受体α (er - α)、孕激素受体(PgR)或表达Ki67抗体的细胞数量。er - α、PgR和Ki67阳性细胞的比例在Lob1中最高,分化程度更高的Lob2和Lob3则逐渐减少。er - α和PgR阳性细胞仅在乳腺上皮中发现,Ki67阴性,而Ki67阳性细胞不表达受体。将这些结果与接种h -3胸腺嘧啶的幼龄处女大鼠乳腺放射自显像er - α和PgR的分布进行比较,测定DNA标记指数(DNA- li)。DNA-LI以及er - α和PgR阳性细胞百分比在顶芽上皮中最高,肺泡芽和小叶中较低。er - α和PgR阳性细胞没有增殖,而那些结合了h -3胸腺嘧啶的细胞对这两种受体都是阴性的。我们的结果使我们得出结论,正常乳腺组织中er - α和PgR的含量随小叶发育程度的变化而变化,与细胞增殖平行。然而,受体的表达发生在增殖细胞以外的细胞中,表明它们至少代表两个独立的细胞群。这些发现为了解雌激素和黄体酮影响乳腺上皮细胞增殖活性的机制,以及它们在导致正常细胞癌变的级联事件启动中的作用开辟了新的途径。
Since cell proliferation is indispensable for the growth and development of the breast, and estrogens are considered to play a major role in promoting cell proliferation, while progesterone influences its differentiation, the present work was designed with the purpose of verifying the relationship between cells containing steroid hormone receptors and proliferating cells in the normal human breast. Twelve breast samples were analyzed for their content of lobules type 1 (Lob1), Lob2, Lob3, and Lob4, and the number of cells containing estrogen receptor alpha (ER-alpha), progesterone receptor (PgR), or expressing Ki67 antibody was determined by double immunocytochemical technique with specific antibodies. The highest percentage of ER-alpha, PgR, and Ki67 positive cells was found in Lob1, with a progressive reduction in the more differentiated Lob2 and Lob3. ER-alpha and PgR positive cells were found exclusively in the breast epithelium and were negative for Ki67, while cells positive for Ki67 did not express receptors. These findings were compared with the distribution of ER-alpha and PgR in the autoradiographs of mammary gland of young virgin rats inoculated with H-3-thymidine for determination of the DNA labeling index (DNA-LI). Both the DNA-LI and the percentage of ER-alpha and PgR positive cells were maximal in the epithelium of terminal end buds, and these values were reduced in alveolar buds and lobules. ER-alpha and PgR positive cells did not proliferate, and those cells that had incorporated H-3-thymidine were negative for both receptors. Our results led us to conclude that the content of ER-alpha and PgR in the normal mammary tissue varies with the degree of lobular development, in parallel with cell proliferation. However, the expression of receptors occurs in cells other than the proliferating cells, indicating that they represent at least two separate cell populations. These findings open new avenues towards the understanding of the mechanisms through which estrogens and progesterone affect the proliferative activity of breast epithelial cells, and their role in the initiation of the cascade of events that leads a normal cell to cancer.