MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

公共卫生服务局题为“2000年健康人”的报告的目标16.3是减少 乳腺癌死亡人数 大量流行病学数据表明， 怀孕与降低乳腺癌风险有关。实验室数据 表明在怀孕期间存在一种独特分子， 可以防止乳腺癌的生长：配体转化的α- 甲胎蛋白（AFP）阻止乳腺癌细胞的生长，无论是在体内 和体外培养。长期目标是通过以下方法阐明其机制： AFP抑制乳腺癌细胞的生长。申请人已经 表达AFP的C-末端结构域，并已证明其 生物活性因此，这位博士预科生的假设 建议不是所有的人AFP结构域III都需要用于 表达其抗肿瘤活性。 有两个具体目标： 1)产生AFP的截短形式（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的生物物理特性。2.）的情况。 去定义最小的- 具有抗肿瘤活性长度类似物。 研究设计 在很大程度上依赖于重组DNA技术和适应性蛋白 表达系统。具体方法是： 通过改造cDNA模板，在杆状病毒中表达蛋白质， 系统，并表征生物和生物物理特性 了产品为了测试抗肿瘤活性，将使用：i.） 抑制雌激素刺激的未成熟小鼠子宫生长， （二）雌激素刺激的MCF-7细胞灶形成的抑制 文化（三）抑制雌激素依赖性MCF-7肿瘤的生长 小鼠异种移植物。

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.