INTERACTION OF HORMONES AND KGF IN MAMMARY GROWTH

描述（改编自申请人的摘要）：长期 这些研究的目的是了解组成和 组织激素/生长因子网络，介导 乳腺中的基质/上皮细胞相互作用。 的 研究人员提出，乳腺激素和角质细胞生长 因子（KGF）构成基质/上皮旁分泌途径的重要 调节正常乳腺上皮细胞的生长， 在激素的肿瘤前和肿瘤生长期间放大 依赖性癌症 假设是乳腺激素调节 上皮细胞对KGF的敏感性，KGF在 在激素敏感性细胞中发生的生长调节改变中的作用 癌前病变和激素依赖性肿瘤。 为了解决这个问题， 研究者提出：1.检查是否正常的敏感性 乳腺上皮对KGF的生长促进作用的改变， 在无血清胶原蛋白凝胶中培养的细胞中的致乳腺癌激素 细胞在其中生长并经历形态发生的培养系统 一个三维矩阵 2.为了检验 癌前病变和激素敏感性肿瘤是由KGF刺激的， 检查这个过程的敏感性是否受到 促乳腺激素 3.测试是否乳房激素调节 通过RNA酶保护上述组织中KGF受体的表达 分析，并通过受体交联碘化生长因子， 培养的细胞，和4.检查肿瘤前病变和激素依赖性 肿瘤表达KGF，如果KGF调节上皮细胞增殖， 在外植体培养或体内的这些组织中。

DESCRIPTION (Adapted from the applicant's abstract): The long term objective of these studies is to understand the composition and organization of hormone/growth factor networks that mediate stromal/epithelial cell interactions in the mammary gland. The investigator proposes that mammogenic hormones and keratinocyte growth factor (KGF) constitute a stromal/epithelial paracrine pathway important for regulation of normal mammary epithelial cell growth that becomes magnified during preneoplastic and neoplastic growth in hormone dependent cancers. The hypothesis is that mammogenic hormones modulate epithelial cell sensitivity to KGF, and that KGF plays a significant role in altered growth regulation occurring in hormone sensitive preneoplasias and hormone dependent tumors. To address this, the investigator proposes : 1. To examine if the sensitivity of normal mammary epithelium to the growth promoting effects of KGF is altered by mammogenic hormones in cells cultured in a serum free, collagen gel culture system in which the cells grow and undergo morphogenesis within a three dimensional matrix. 2. To examine if the growth of preneoplasias and hormone sensitive tumors is stimulated by KGF, and to examine whether the sensitivity of this process is modulated by mammogenic hormones. 3. test whether mammogenic hormones modulate the expression of KGF receptor in the above tissues by RNAse protection analysis, and by receptor cross linking to iodinated growth factor in cultured cells, and 4. examine if preneoplasias and hormone dependent tumors express KGF, and if KGF regulates epithelial cell proliferation in these tissues in explant culture or in vivo.