ROLE OF STROMA IN MAMMARY GLAND CELL PROLIFERATION

这项研究的目的是提供对以下方面的洞察 乳腺上皮-基质细胞相互作用对雌激素的影响 黄体酮和/或孕酮诱导正常小鼠乳腺的增殖 腺体。尤其令人感兴趣的是确定间质 影响会影响正常和癌症患者的激素独立性 乳房组织。上皮-间质的关系 相互作用和荷尔蒙调节将在体内进行分析 并在体外通过比较不同乳腺发育情况 表现出不同程度的激素独立性的阶段。在……里面 所有病例的上皮和间质细胞的增殖情况将进行评估。 细胞进行DNA组织放射自显影。对激素受体的影响 监管将通过配体结合分析、类固醇进行监测 放射自显影，或使用抗激素受体的免疫细胞化学 抗体。 通过活体实验，我们打算确定雌激素和/或 黄体酮是直接作用的有丝分裂原，如果它们间接作用的话 通过局部旁分泌或自分泌生长因子或全身生长 表皮生长因子或转化生长因子等因素 各种因素。 我们将确定雌激素和/或黄体酮是否诱导 增殖与雌激素或雌激素的存在有关 上皮细胞或间质细胞中的孕激素受体。 我们还将确定一个人是否可以改变体内的激素反应 通过操纵基质环境而活着。 从体外，细胞培养研究，我们打算识别细胞， 基质细胞影响的生化和分子机制 荷尔蒙反应。上皮细胞和间质细胞将 身体上彼此分开，并进一步被解剖成 它们的生化和分子组成。重组将会 被实验操纵以识别特定类型的 基质细胞参与、细胞接触和溶解的作用 激素依赖性增殖的因素。生物化学 细胞外基质的组成对 乳蛋白的激素调控基因表达。类似 生物化学和分子方法将被应用于研究 细胞外基质与细胞增殖。的长期目标是 这些研究是为了阐明激素的生物学基础。 独立性并为激素的治疗提供了理论基础 独立的人类乳腺癌。

The objective of the study is to provide insight into ways in which mammary epithelial-stromal cell interactions influence estrogen and/or progesterone-induced proliferation in normal mouse mammary gland. Of particular interest is to determine how stromal influences can affect hormone independence in normal and cancerous mammary tissue. The relationship between epithelial-stromal interactions and hormonal regulation will be analyzed both in vivo and in vitro by comparing different mammary gland development stages that exhibit varying degrees of hormone independence. In all cases proliferation will be assessed in epithelial and stromal cells by DNA histoautoradiography. The effects on hormone receptor regulation will be monitored by ligand binding assays, steroid autoradiography, or immunocytochemistry using anti-hormone receptor antibodies. From in vivo experiments we intend to determine if estrogen and/or progesterone are direct acting mitogens or if they act indirectly via local paracrine or autocrine growth factors or systemic growth factors such as epidermal growth factor or transforming growth factors. We will determine if estrogen and/or progesterone induced proliferation are correlated with the presence of estrogen or progesterone receptors in epithelial cells or stromal cells. We will also determine if one can alter hormonal responsiveness in vivo by manipulating the stromal environment. From in vitro, cell culture studies we intend to identify cellular, biochemical and molecular mechanisms by which stromal cells affect hormone responsiveness. Epithelial cells and stromal cells will be physically separated from one another and further dissected into their biochemical and molecular components. Reconstitution will be experimentally manipulated to identify the specific types of stromal cells involved, the roles of cell contact and soluble factors in hormone dependent proliferation. The biochemical composition of the extracellular matrix has a profound effect on hormonally regulated gene expression of milk proteins. Similar biochemical and molecular methods will be applied to the study of extracellular matrix and proliferation. The long term goal of these studies is to elucidate the biological basis of hormone independence and provide a rationale for treatment of hormone independent human mammary cancer.