ROLE OF STROMA IN MAMMARY GLAND CELL PROLIFERATION

这项研究的目的是提供深入了解的方式， 乳腺上皮-基质细胞相互作用影响雌激素 和/或孕酮诱导的正常小鼠乳腺增生 腺。 特别感兴趣的是确定基质如何 影响可以影响正常人和癌症患者的激素独立性 乳腺组织 上皮-间质细胞的关系 相互作用和激素调节将在体内分析， 并通过比较不同乳腺发育的体外实验 表现出不同程度的激素依赖性的阶段。 在 所有病例的增殖将在上皮和间质中进行评估。 细胞DNA组织放射自显影。 对激素受体的影响 调节将通过配体结合测定、类固醇 放射自显影或使用抗激素受体的免疫细胞化学 抗体的 从体内实验中，我们打算确定雌激素和/或 孕酮是直接作用的有丝分裂原， 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 因素 我们将确定是否雌激素和/或孕激素诱导 增殖与雌激素的存在相关， 上皮细胞或基质细胞中的孕酮受体。 我们还将确定是否可以改变激素反应， 体内通过操纵基质环境。 从体外细胞培养研究中，我们打算鉴定细胞， 间质细胞通过其生物化学和分子机制 激素反应 上皮细胞和基质细胞将 在物理上彼此分离，并进一步分解成 它们的生物化学和分子组成。 重组将 通过实验操作来识别特定类型的 基质细胞参与，细胞接触和可溶性的作用 激素依赖性增殖的因素。 生化 细胞外基质的组成对 乳蛋白质的经尿道调节的基因表达。 类似 生物化学和分子生物学方法将被应用于研究 细胞外基质和增殖。 的长期目标 这些研究旨在阐明激素的生物学基础， 并为激素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.