MAMMARY GROWTH REGULATION: TRANSFORMING GROWTH FACTOR-B

乳房生长调节：转化生长因子-B

• 批准号: 3329512
• 负责人: CHARLES W DANIEL
• 金额: $ 17.67万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3329512
• 关键词: DNA replication; autoradiography; breast neoplasms; cell differentiation; cell growth regulation; complementary DNA; drug administration rate /duration; gel electrophoresis; growth inhibitors; histogenesis; hormone regulation /control mechanism; immunoprecipitation; laboratory mouse; laboratory rabbit; mammary epithelium; mammary gland; neoplastic growth; nucleic acid hybridization; nucleic acid probes; preneoplastic state; radioimmunoassay; radiotracer; tissue /cell culture; transforming growth factors

We have recently obtained the first evidence for a possible inhibitory role in vivo for Transforming Growth Factor-Beta (TGF-Beta), a peptide previously identified with a variety of effects on cultured cells, including inhibition of proliferation of various epithelia in culture. Using small plastic "Elvax" implants capable of sustained, local release of TGF-Beta when implanted directly into tissues, we found that TGF-Beta dramatically inhibited the growth of mammary ducts in vivo. The effect was fully reversible and appeared in all respects to mimic the natural process of growth regulation in the gland. Inhibition of cell proliferation by tissue factors in thought to be a major, though poorly understood homeostatic influence operating in normal tissue growth and maintenance. This negative growth regulation is of special significance to the cancer problem; a critical feature of malignant cells is their ability to proliferate in the presence of regulative influences that restrain the growth of normal cells. Using the mammary-Elvax system to provide a quantitative measure of growth regulation, we propose to expand our preliminary findings as follows: 1. Characterize growth regulation by TGF-Beta, obtaining data on the time course, dose-dependency, reversibility, and other features of inhibition. Precancerous and cancerous mammary tissues will be studied as well as several normal growth stages. 2. Mechanisms of growth inhibition will be investigated by examining interactions of TGF-Beta with other growth factors and hormones, and by determining receptor localization and ligand binding characteristics. 3. The hypothesis that TGF-Beta is a naturally occurring growth regulator in the mammary gland will be tested. Its production in vivo and in cultured mammary cells will be directly assayed, and TGF-Beta gene activity will be determined. Using specific antibody released locally from Elvax implants, the effects of neutralization will be determined. Influences of TGF-Beta on cell differentiation and on epithelial-stroma relations will be investigated.

我们最近获得了可能的第一个证据 在体内转化生长因子β的抑制作用 （tgf-beta），先前用多种肽鉴定的肽 对培养细胞的影响，包括抑制的增殖 文化中各种上皮。 使用小型塑料“ Elvax”植入物 植入时能够持续的局部释放TGF-beta 直接进入组织，我们发现TGF-beta急剧 抑制体内乳腺导管的生长。 效果是 完全可逆，并且在模仿自然的各个方面出现 腺体中生长调节的过程。 通过组织因素抑制细胞增殖是一种 专业，虽然了解稳态的影响不足 在正常的组织生长和维持中。 这种负面的增长 调节对癌症问题具有特殊意义。一个 恶性细胞的关键特征是它们在 限制的监管影响的存在 正常细胞。 使用乳腺 - 藻类系统提供 我们建议扩大生长调节的定量度量 我们的初步发现如下： 1。通过TGF-beta来表征生长调节，获取数据 在时间过程中，剂量依赖性，可逆性和其他 抑制作用。 癌性乳腺癌 将研究组织以及几个正常的生长阶段。 2。将研究生长抑制的机制 检查TGF-β与其他增长因子的相互作用 和激素，以及确定受体定位和配体 结合特征。 3。假设TGF-beta是天然存在的生长 将测试乳腺中的调节剂。 它的生产 体内和培养的乳腺细胞将被直接分析，并且 将确定TGF-β基因活性。 使用特定 抗体是从猫植入物局部释放的 将确定中和。 TGF-β对细胞的影响 分化和上皮关系的关系将是 调查。