An in vitro long-term culture model for normal human mammary gland: expression and regulation of steroid receptors
An in vitro long-term culture model for normal human mammary gland: expression and regulation of steroid receptors
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DOI：
10.1007/s00441-002-0683-z
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发表时间：
2003-02-01
影响因子：
3.6
通讯作者：
Ylikomi, T
中科院分区：
文献类型：
--
作者：
Zhuang, YH;Saaristo, R;Ylikomi, T
类固醇及其核受体在人类乳腺（HMG）正常功能的发育和维持中起着至关重要的作用。它们也与乳腺癌发生有关。然而，类固醇在正常HMG中的作用的研究受到实验困难的阻碍。利用一种新建立的体外长期培养方法，我们成功地培养了正常HMG组织超过2个月，而不损害其形态学或类固醇受体表达。细胞结构和细胞外基质蛋白的表达与培养前相似，HMG组织保留了其类固醇受体表达和调节的特性。添加17-β雌激素乳腺组织显着增加孕激素受体（PR）的表达，但只有轻微的影响，雌激素受体（ER）。醋酸甲羟孕酮在24-48 h内下调PR的表达，同时上调雄激素受体的表达。当HMG组织培养在培养基中含有正常或葡聚糖包被的活性炭剥离胎牛血清或正常人血清，类固醇激素受体的表达和调节是相似的，但在程度上不同。去血清组1周后HMG形态基本正常，但ER、PR的表达和调节发生改变。因此，由于HMG保留了在培养中表达类固醇受体的能力，因此这种长期培养系统可能是研究类固醇对乳腺调节的良好模型。
Steroids and their nuclear receptors play crucial roles in the development and maintenance of normal functions of the human mammary gland (HMG). They have also been implicated in breast carcinogenesis. However, the study of steroid action in normal HMG has been hampered by experimental difficulties. By using a newly established in vitro long-term culture method, we successfully cultured normal HMG tissue for more than 2 months without detriment to its morphology or steroid receptor expression. Expression of the cellular structural and extracellular matrix proteins was similar to that prior to culture, and HMG tissue retained its properties of steroid receptor expression and regulation. Addition of 17-beta estrogen to mammary tissues markedly increased the expression of progesterone receptor (PR) but only slightly affected that of the estrogen receptor (ER). Medroxyprogesterone acetate down-regulated the expression of PR within 24-48 h and also increased the expression of androgen receptor. When HMG tissue was cultured in medium containing normal or dextran-coated charcoal-stripped fetal calf serum or normal human serum, the expression and regulation of steroid hormone receptors were similar, although different in extent. When serum was omitted, the morphology of HMG was normal after I week, but the expression and regulation of ER and PR were altered. Thus, as HMGs retain the capacity to express steroid receptors in culture, this long-term culture system is probably a good model for studying the regulation of the mammary gland by steroids.