ROLE OF STROMA IN MAMMARY GLAND CELL PROLIFERATION

基质在乳腺细胞增殖中的作用

• 批准号: 3179634
• 负责人: SANDRA Z HASLAM
• 金额: $ 9.15万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179634
• 关键词: autoradiography; cell growth regulation; estrogens; growth /development; hormone regulation /control mechanism; immature animal; lactation; mammary epithelium; mammary gland; progesterone; radiotracer; stromal cells

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)

我们观察到，正常小鼠乳腺，不像某些人， 和啮齿动物乳腺肿瘤，也可能变得难以治疗 乳腺依赖性生长调节;然而，与乳腺癌相反， 在正常乳腺中，这种不应性是完全可逆的。 雌激素和孕激素是乳腺癌的两种主要生长调节激素 腺，被认为是通过产生其生物效应， 受体介导的机制。 雌激素受体的最新研究 子宫内的个体发育表明受体出现在基质中， 在它们出现在上皮细胞之前。 然而， 当受体仅存在于基质中时，组织会导致 上皮细胞增殖。 已经假设 基质细胞中的垂体诱导的生长因子负责 上皮细胞的生长。 拟议研究的具体目标是 确定是否通过雌激素和/或 乳腺中的孕酮直接响应这些激素 或者它是否由基质细胞的反应间接介导。 第一步将是确定雌激素（ER）的分布， 孕酮受体（PgR）在各种上皮和基质细胞 构成乳腺结构范围的类型。 乳腺 在不同的发育阶段，对雌激素的反应不同， 孕激素将检查：（1）出生后早期腺体将 研究以确定上皮细胞中ER和PgR的个体发生， 基质细胞与细胞增殖反应的个体发生 雌激素和孕激素;（2）成年处女腺将作为一个研究， 对雌激素和雌激素的细胞增殖作用高度敏感的状态 和孕酮;和（3）产后腺体将研究潜在的 ER和/或PgR的细胞分布的变化可能解释了 在哺乳期观察到的对生长调节的顽固性。 ER和PgR的细胞定位将通过组织学方法确定， 类固醇放射自显影技术 对于所有的发展 响应雌激素治疗的体内细胞增殖阶段，或 孕酮将通过DNA历史放射照相术平行定量。 这些研究将提供重要的见解的作用，基质和 上皮细胞介导和/或改变生长调节， 雌激素和/或孕激素，生长不应性的基础 乳腺癌的调节，以及激素的治疗逆转 在人类乳腺癌中的独立性。 （丁）