Interferon and Raloxifene Effects on Cancer Cells

描述（由申请人提供）：Cheryl Rosenfeld博士，申请人，拥有D.V.M.（伊利诺伊大学厄巴纳-香槟分校，1995年），并在密苏里州接受了两年的解剖病理学住院医师培训。随后，她跟随Dennis Lubahn博士完成了动物科学博士学位，研究雌性激素受体- α基因缺失小鼠（ERaKO小鼠）卵巢和生殖道异常。她目前是一名研究助理教授，她的发起人R. Michael Roberts博士是密苏里州策展人教授，也是美国国家科学院的成员。Roberts博士的研究兴趣是母体对妊娠的识别，特别是I型干扰素（ifn）在大型农场哺乳动物妊娠早期所起的作用。罗森菲尔德博士一直在研究绵羊子宫内IFN受体亚基的结构和分布，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讲师。罗森菲尔德博士是七篇评审论文的第一作者，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通过转录上调子宫内膜中雌激素受体- β (erβ)基因的活性，从而调节雌激素受体- α (ERa)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，无论是单独使用还是与抗雌激素联合使用，是否有治疗人类子宫癌的潜力。这项工作将包括研究IFN对细胞增殖和凋亡的影响，以及对源自子宫内膜癌的细胞中ERa和ERb的调节，确定ERb表达的转录控制的实验，以及比较IFN对ERa或ERb无效小鼠子宫内基因表达影响的微阵列实验。当罗森菲尔德博士获得正式职位后，所有这些工作都可以转移。密苏里大学在生殖生物学方面有一个杰出的项目，其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。这所大学正在发展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，罗森菲尔德博士有望在其中继续茁壮成长。

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.