Interferon and Raloxifene Effects on Cancer Cells

描述（由申请人提供）： 申请人谢丽尔·罗森菲尔德医生有脑血管畸形（伊利诺伊大学厄巴纳-香槟分校1995年）和两年的解剖病理学住院医师培训在密苏里州。 她完成了博士学位。与Dennis Lubahn博士在《动物科学》杂志上讨论了雌激素受体α基因缺失小鼠（ERaKO小鼠）的卵巢和生殖道异常。 她目前是一个研究助理教授与她的赞助商为这项建议，博士R。迈克尔·罗伯茨是密苏里州的馆长教授，也是国家科学院的成员。 罗伯茨博士的兴趣是母亲对怀孕的认识，特别是在大型农场哺乳动物怀孕早期I型干扰素（IFN）所起的作用。 Rosenfeld博士一直在研究绵羊子宫内IFN受体亚单位的结构和分布，这是她的主要项目。 她目前有25%的承诺作为兽医显微解剖学的讲师。 Rosenfeld博士是七篇经评审论文的第一作者，并是另外八篇论文的合著者。 她的目标是获得终身教职，这将使她能够在癌症生物学和比较医学方面进行教学和研究。 支持这一建议的假设是I型IFN转录上调子宫内膜中雌激素受体β（ER β）基因的活性，这反过来调节雌激素受体α（ER α）的浓度。 这些实验的总体目标是证明这一假设，并确定I型IFN单独或与抗雌激素组合是否具有治疗人类子宫癌的任何潜力。 这项工作将涉及对细胞增殖和凋亡的影响，并对来自子宫内膜癌的细胞中的ER a和ER b的调节的研究，确定ER b表达的转录控制的实验，以及比较IFN对ER a或ER b无效的小鼠子宫中基因表达的影响的微阵列实验。 当罗森菲尔德博士获得永久职位时，所有这些工作都是可以转让的。 密苏里州大学在生殖生物学方面有一个杰出的项目，教师从事癌症生物学和内分泌干扰，以及生化内分泌学和遗传学的研究。 该大学正在开发一个比较肿瘤学项目。 校园提供了丰富的学科组合和协作环境，罗森菲尔德博士预计将继续蓬勃发展。

DESCRIPTION (provided by applicant): Dr. Cheryl Rosenfeld, the applicant, has a D.V.M. (University of Illinois, Urbana-Champaign 1995) and two years of Anatomical Pathology residency training at Missouri. She then completed a Ph.D. in Animal Sciences with Dr. Dennis Lubahn on abnormalities in the ovaries and reproductive tract of mice null for the estrogen receptor-alpha gene (ERaKO mouse). She is currently a Research Assistant Professor with her sponsor for this proposal, Dr. R. Michael Roberts, a Curators' Professor at Missouri and member of the National Academy of Sciences. Dr. Roberts' interests are maternal recognition of pregnancy and particularly in the role that is played by Type I interferons (IFNs) in early pregnancy of the large farm mammals. Dr. Rosenfeld has been studying the structure and distribution of IFN receptor subunits within the uterus of the sheep as her primary project. She currently has a 25% commitment as an instructor in Veterinary Microanatomy. Dr. Rosenfeld is the first author on seven refereed papers and a co-author on eight more. Her goal is to obtain a tenure track faculty position that will allow her to conduct teaching and research in cancer biology and comparative medicine. The hypothesis that underpins this proposal is that Type I IFN transcriptionally up-regulate the activity of the estrogen receptor-beta (ERbeta) gene in endometrium, which in turn modulates the concentration of the estrogen receptor-alpha (ERa). The overall objective of these experiments is to prove this hypothesis and determine whether type I IFN, either alone or in combination with an anti-estrogen, have any potential for treating human uterine cancers. The work will involve a study of effects on cell proliferation and apoptosis and on the regulation or ERa and ERb in cells derived from endometrial cancers, experiments to determine the transcriptional control of ERb expression, and microarray experiments to compare the effects of IFN on gene expression in the uteri of mice null for either ERa or ERb. All of this work is transferable when Dr. Rosenfeld takes a permanent position. The University of Missouri has an outstanding program in reproductive biology, with faculty working in cancer biology and endocrine disruption, as well as biochemical endocrinology and genetics. The University is in the process of developing a Comparative Oncology Program. The campus provides a rich mix of disciplines and a collaborative environment, in which Dr. Rosenfeld is expected to continue to thrive.