权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

PHOSPHATIDYLETHANOLAMINE AND CELL PROLIFERATION

磷脂酰乙醇胺和细胞增殖

基本信息

批准号：
3169300
负责人：
T KANO-SUEOKA
金额：
$ 18.27万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-07-01 至 1993-02-28
项目状态：
已结题

项目摘要

The long term objective of our research is to understand the regulatory mechanisms of proliferation and differentiation of normal and neoplastic mammary epithelial cells. Mammalian cells in culture can be classified as ethanolamine (Etn)-responsive or - nonresponsive with regard to their growth. Normal mammary cells are Etn-responsive and some neoplastic mammary cells are also Etn- responsive, whereas other neoplastic mammary cells are Etn- nonresponsive. In Etn-responsive cells de novo biosynthesis of phosphatidylethanolamine (PE) is limited due to the reduced activity of the serine exchange enzyme which is responsible for the biosynthesis of the precursor of PE, phosphatidylserine (PS). When the medium is not supplemented with Etn, the membrane phospholipid in Etn-responsive cells becomes PE-deficient, the proliferation stops. The immediate objective is to elucidate the biochemical mechanism of Etn-responsive and -nonresponsiveness of mammary cells and to identify the gene or genes responsible for conferring to the cells Etn-nonresponsiveness. The present proposal has three specific aims. The first aim is to elucidate the cause of the reduced activity of the serine exchange enzyme in Etn-responsive cells. The reduced activity of the enzyme does not seem to result from a limited amount of enzyme, but rather results from an actual reduction in activity. The properties of the enzyme will be examined using crude cell extract and the microsomal fraction. The second aim is to analyze the effect of PE-deficiency on extracellular signal transductions in order to elucidate the mechanism of cessation of cell proliferation due to PE-deficiency. We already have clear indications that a signal transduction mediate by tumor promoting phorbol esters and EGF receptor does not proceed properly. Further analyses of binding characteristics of EGF and insulin will be carried out. The third aim is to identify and isolate the gene (or genes) which renders the cell Etn-nonresponsive. This aim will be accomplished by 1) studying int-1 and int-2 oncogenes which have initially been shown to convert Etn-responsive cells to -nonresponsive, and 2) isolating DNA fragment from an Etn-nonresponsive human breast carcinoma cell line by transfection of Etn-responsive rat carcinoma cells. These studies will contribute to the understanding of the role of membrane phospholipids in various cellular metabolic processes and the process of malignant tumor progression.

我们研究的长期目标是了解增殖和分化的调控机制正常和肿瘤性乳腺上皮细胞。哺乳动物细胞培养物中的细菌可分为乙醇胺 (Etn) 反应性或 - 对它们的生长没有反应。正常乳腺细胞是 Etn 反应性的，一些肿瘤性乳腺细胞也是 Etn 反应性的反应性的，而其他肿瘤性乳腺细胞是 Etn- 无反应。在 Etn 反应细胞中从头生物合成磷脂酰乙醇胺（PE）由于减少而受到限制丝氨酸交换酶的活性负责 PE 前体磷脂酰丝氨酸 (PS) 的生物合成。什么时候培养基未添加 Etn（膜磷脂）在 Etn 反应性细胞中，PE 缺乏，增殖停止。近期目标是阐明生物化学乳腺细胞 Etn 反应性和非反应性的机制并鉴定负责赋予细胞Etn-无反应性。目前的提案有三点具体目标。第一个目的是阐明导致活性降低的原因。 Etn 反应细胞中的丝氨酸交换酶。减少的酶的活性似乎不是由有限的酶量，而是实际减少的结果活动。将使用以下方法检查酶的特性：粗细胞提取物和微粒体部分。第二个目的是分析 PE 缺乏对细胞外信号转导以阐明 PE缺陷导致细胞增殖停止的机制。我们已经有明确的迹象表明信号转导由促进肿瘤的佛波酯介导，而 EGF 受体则不介导正确进行。结合特性的进一步分析将进行EGF和胰岛素。第三个目标是鉴定和分离基因（或多个基因）使细胞 Etn 无反应。这个目标一定会实现 1) 研究最初已被证实的 int-1 和 int-2 癌基因显示可将 Etn 反应细胞转化为无反应细胞，以及 2) 从 Etn 无反应的人类乳房中分离 DNA 片段转染 Etn 反应性大鼠癌细胞系细胞。这些研究将有助于理解各种细胞代谢过程中的膜磷脂恶性肿瘤的进展过程。