MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

PHS报告《2000年健康人群》的目标16.3是减少 乳腺癌死亡人数。大量的流行病学数据表明 怀孕与降低乳腺癌风险有关。实验室数据 表明在怀孕期间有一种独特的分子存在 可以预防乳腺癌的生长：配体转化的α- 甲胎蛋白(AFP)可在体内阻止乳腺癌细胞的生长 而且是在体外。长期目标是通过以下方式阐明这一机制 哪种AFP可以抑制乳腺癌细胞的生长。申请人有 表达了甲胎蛋白的C-末端结构域，并展示了其 生物活性。因此，这位博士后的假设 建议并不是所有的人类甲胎蛋白III区都是必需的 其抗肿瘤活性的表达。有两个具体目标： 1)产生截短形式的AFP(结构域III)。目标 包括：在抗肿瘤试验中评价生物活性， 评估对配体(雌激素)的需求，并表征 AFT结构域III的生物物理性质。2.)为了定义最小的- 具有抗肿瘤活性的长度类似物。研究设计 严重依赖重组DNA技术和适应性蛋白质 表达系统。具体的方法是：产生所需的类比 通过设计cDNA模板，在杆状病毒中表达蛋白质 系统，并表征其生物学和生物物理性质。 这些产品。为了测试抗肿瘤活性，将使用：i.) 抑制雌激素刺激的幼鼠子宫生长， II.)雌激素对人乳腺癌MCF-7细胞集落形成的抑制作用 文化和三)。)雌激素依赖性MCF-7肿瘤生长抑制作用的实验研究 小鼠的异种移植。

Objective 16.3 of the PHS report "Healthy People 2000" is to reduce breast cancer deaths. Substantial epidemiological data suggest that pregnancy is associated with reduced breast cancer risk. Laboratory data indicate that there is a molecule present uniquely during pregnancy which can prevent the growth of breast cancer: ligand-transformed alpha- fetoprotein(AFP) stops the growth of breast cancer cells, both in vivo and in vitro. The long-term objective is to elucidate the mechanism by which AFP arrests the growth of breast cancer cells. The applicant has expressed the C-terminal domain of AFP and has demonstrated its biological activity. Therefore, the hypothesis of this predoctoral proposal is that not all of Domain III of human AFP is required for expression of its anti-oncotic activity. There are two Specific Aims: 1) To produce a truncated form of AFP(Domain III). The objectives include: evaluating the biological activity in anti-oncotic assays, evaluating the requirement for ligand (estrogen), and characterizing the biophysical properties of Domain III of AFT. 2.) To define the minimal- length analog which possess anti-oncotic activity. The research design relies heavily on recombinant DNA technology and adaptable protein expression systems. The specific methods are: to produce desired analogs by engineering cDNA templates, to express proteins in a baculovirus system, and to characterize the biological and biophysical properties of the products. To test for anti-oncotic activity, will be used: i.) inhibition of estrogen-stimulated uterine growth of the immature mouse, ii.) inhibition of estrogen-stimulated foci formation of MCF-7 cells in culture and iii.) inhibition of growth of estrogen-dependent MCF-7 tumor xenografts in mice.