ROLE OF STROMA IN MAMMARY GLAND CELL PROLIFERATION

我们观察到正常的小鼠乳腺，就像某些人类 和啮齿动物乳腺肿瘤，也可以变得难治性 激素依赖的生长调节；然而，与乳房相反 肿瘤，在正常乳腺中，这种不稳定是完全可逆的。 雌激素和孕酮--乳腺中的两种主要生长调节激素 腺体，被认为通过 激素受体介导的机制。雌激素受体的研究近况 子宫的个体发育研究表明，受体出现在间质中 在它们出现在上皮细胞之前。然而，接触到的荷尔蒙 当受体仅存在于基质中时，组织会导致 上皮细胞增殖。据推测， 荷尔蒙诱导的基质细胞生长因子是导致 上皮细胞的生长。拟议研究的具体目的是 确定雌激素和/或雌激素对上皮细胞增殖的调节作用 乳腺中的黄体酮是对这些激素的直接反应。 或者它是否是由基质细胞的反应间接调节的。 第一步是确定雌激素(ER)和 孕激素受体(PGR)在多种上皮和基质细胞中的表达 构成乳腺结构范围的类型。乳腺 在不同的发育阶段对雌激素和 孕酮将被检查：(1)出生后早期腺体 上皮性卵巢癌组织中雌激素受体和前列腺素受体的个体发育研究 基质细胞与细胞增殖反应的个体发育 对雌激素和黄体酮的作用；(2)成年处女腺将作为 对两种雌激素的细胞增殖效应的高度反应状态 和黄体酮；以及(3)产后腺的潜力将被研究 ER和/或PGR细胞分布的变化可能解释 在哺乳期间观察到的对生长调节的不稳定。 ER和PGR的细胞定位将由组织学决定 类固醇放射自显影技术。对于所有发展中的 雌激素或雌激素治疗对体内细胞增殖的影响 黄体酮将同时通过DNA历史放射摄影术进行定量。 这类研究将为基质和细胞外基质的作用提供重要的见解。 上皮细胞在调节和/或调节生长中的作用 雌激素和/或黄体酮，生长不稳定的基础 乳腺癌的调控与激素的治疗逆转 在人类乳腺癌中的独立性。(D)

We have observed that normal mouse mammary gland, not unlike certain human and rodent mammary neoplasias, can also become refractory to hormone-dependent growth regulation; however, in contrast to mammary tumors, in normal mammary gland this refractoriness is fully reversible. Estrogen and progesterone, two major growth regulatory hormones in mammary gland, are believed to produce their biologic effects via hormone-receptor-mediated mechanisms. Recent studies of estrogen receptor ontogeny in the uterus have shown that receptors appear in the stroma before they appear in the epithelium. However, hormone exposure of the tissue at a time when receptors are present only in the stroma results in cell proliferation in the epithelium. It has been hypothesized that hormonally-induced growth factors in stromal cells are responsible for the growth of the epithelium. The specific aim of the proposed research is to determine if regulation of epithelial cell proliferation by estrogen and/or progesterone in mammary gland occurs directly in response to these hormones or whether it is mediated indirectly by the response of the stromal cells. The first step will be to determine the distribution of estrogen (ER) and progesterone receptors (PgR) in the various epithelial and stromal cell types that make up the range of mammary gland structures. Mammary glands at different developmental stages with differing responses to estrogen and progesterone will be examined: (1) early postnatal gland will be investigated to determine the ontogeny of ER and PgR in epithelial and stromal cells in relation to the ontogeny of cell proliferative responses to estrogen and progesterone; (2) adult virgin gland will be studied as a highly responsive state to the cell proliferative effects of both estrogen and progesterone; and (3) postpartum gland will be studied for potential changes in cellular distribution of ER and/or PgR that could account for the refractoriness to growth regulation that is observed during lactation. Cellular localization of ER and PgR will be determined histologically by the technique of steroid autoradiography. For all of the developmental stages in vivo cell proliferation in response to treatment with estrogen or progesterone will be quantitated, in parallel, by DNA historadiography. Such studies will provide important insights into the roles of stromal and epithelial cells in mediating and/or modifying growth regulation by estrogen and/or progesterone, the basis for refractoriness to growth regulation in mammary cancer, and the therapeutic reversal of hormone independence in human mammary cancer. (D)