HUMAN BREAST CANCER CELL GROWTH INHIBITION BY VITAMIN E

维生素 E 抑制人类乳腺癌细胞生长

基本信息

批准号：
2100345
负责人：
KIMBERLY KLINE
金额：
$ 12.23万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1997-07-31
项目状态：
已结题

项目摘要

Long term goals of our lab are to better understand the biological actions of vitamin E compounds at the cellular and molecular levels in normal and cancerous states. Studies in our lab show that a succinate derivative of natural vitamin E (RRR-alpha-tocopherol) referred to as vitamin E succinate (RRR-alpha-tocopheryl succinate; VES) is capable of inhibiting the proliferation of human breast cancer cells in culture. Previous studies by our lab demonstrating that VES inhibits the proliferation of human breast cancer cells by the induction of autocrine acting growth- inhibitory factors, one of which is tumor growth factor-beta (TGF-beta), represent a major conceptual advance in the understanding of growth regulation by vitamin E compounds. Proposed studies will use estrogen receptor-positive (ER+) and estrogen receptor negative (ER-) human breast cancer cells as experimental models to further investigate the mechanisms whereby VES is causing growth inhibition. Specific objectives are to characterize the connection between VES's ability to inhibit human breast cancer cell proliferation and its effects on the expression of TGF-beta subtype expression and activation and TGF-beta receptor expression. The proposed studies will increase basic knowledge about biological actions of VES and will document how VES is inducing the secretion of biologically active TGF- betas by breast cancer cells and how VES is enhancing the growth inhibitory actions of exogenous TGF-betas on breast cancer cell proliferation. These studies are critical for generating important information that will be useful in designing in vivo studies for testing the potential chemopreventative and chemotherapeutic use of VES in treatment of human breast cancer.

我们实验室的长期目标是更好地了解生物行为维生素 E 化合物在正常和分子水平的细胞和分子水平癌症状态。我们实验室的研究表明，琥珀酸衍生物天然维生素E（RRR-α-生育酚）简称维生素E 琥珀酸酯（RRR-α-生育酚琥珀酸酯；VES）能够抑制人类乳腺癌细胞在培养物中的增殖。以前的我们实验室的研究表明，VES 可以抑制增殖人类乳腺癌细胞通过诱导自分泌作用生长- 抑制因子，其中之一是肿瘤生长因子-β（TGF-β），代表了理解增长的重大概念进步维生素E化合物的调节。拟议的研究将使用雌激素受体阳性 (ER+) 和雌激素受体阴性 (ER-) 人乳腺癌细胞作为实验模型进一步研究其机制 VES 会导致生长抑制。具体目标是描述 VES 抑制人类乳腺能力之间的联系癌细胞增殖及其对TGF-β表达的影响亚型表达和激活以及 TGF-β 受体表达。拟议的研究将增加生物学的基础知识 VES 的行动和意愿记录 VES 如何诱导具有生物活性的 TGF-的分泌乳腺癌细胞的 beta 以及 VES 如何促进生长外源性TGF-β对乳腺癌细胞的抑制作用增殖。这些研究对于产生重要的有助于设计体内测试研究的信息 VES 的潜在化学预防和化疗用途治疗人类乳腺癌。