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INTERACTION OF HORMONES AND KGF IN MAMMARY GROWTH

激素和 KGF 在乳房生长中的相互作用

基本信息

批准号：
2458198
负责人：
Walter T. Imagawa
金额：
$ 16.04万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-08-01 至 2000-07-31
项目状态：
已结题

项目摘要

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.

描述(改编自申请人的摘要)：长期这些研究的目的是了解其组成和调节激素/生长因子网络的组织乳腺间质/上皮细胞的相互作用。这个研究人员提出，促乳腺激素与角质形成细胞生长因子(KGF)构成间质/上皮旁分泌途径的重要途径为了调节正常的乳腺上皮细胞的生长癌前病变和肿瘤生长过程中激素的放大依赖型癌症。假设是生乳荷尔蒙调节上皮细胞对KGF的敏感性，以及KGF在其中的重要作用激素敏感型患者生长调节改变中的作用创业和激素依赖型肿瘤。为了解决这个问题，研究人员建议：1.检查是否正常的敏感度乳腺上皮对KGF促生长作用的影响无血清胶原凝胶培养细胞中的促乳腺激素细胞在其中生长和进行形态发生的培养系统一个三维矩阵。2.检查是否增长了 KGF刺激创业和激素敏感型肿瘤，并检查这一过程的敏感性是否受生乳房的激素。3.测试促乳房激素是否调节核糖核酸酶保护下KGF受体在上述组织中的表达分析，并通过受体与碘化生长因子在培养的细胞，以及4.检查创业和激素依赖肿瘤表达KGF，KGF是否调控上皮细胞增殖在这些组织中，无论是外植体培养还是体内。