Interferon and Raloxifene Effects on Cancer Cells

干扰素和雷洛昔芬对癌细胞的影响

• 批准号: 6787639
• 负责人: Cheryl Susan Rosenfeld
• 金额: $ 12.57万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6787639
• 关键词: RNase protection assay; apoptosis; cell proliferation; endometrium; estrogen receptors; gene deletion mutation; gene expression; gene targeting; genetic regulatory element; genetic transcription; genetically modified animals; hormone regulation /control mechanism; interferons; laboratory mouse; microarray technology; neoplasm /cancer pharmacology; neoplastic cell; raloxifene; receptor expression; reporter genes; site directed mutagenesis; tissue /cell culture; transcription factor; uterus neoplasms; western blottings

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.

描述(申请人提供)：谢丽尔·罗森菲尔德博士，申请人，拥有医学博士学位(伊利诺伊大学厄巴纳-香槟分校，1995)，并在密苏里州接受过两年的解剖病理学住院医师培训。然后，她与Dennis Lubahn博士一起完成了动物科学博士学位，研究雌激素受体-α基因缺失的小鼠卵巢和生殖道异常(ERaKO小鼠)。她目前是一名研究助理教授，她的赞助人R·迈克尔·罗伯茨博士是密苏里州的策展人教授，也是国家科学院的成员。罗伯茨博士感兴趣的是母体对怀孕的认识，特别是I型干扰素(IFN)在大型农场哺乳动物早期怀孕中所起的作用。罗森菲尔德博士一直在研究绵羊子宫内干扰素受体亚单位的结构和分布，这是她的主要项目。作为一名兽医显微解剖学讲师，她目前有25%的承诺。罗森菲尔德博士是7篇被审阅论文的第一作者，也是另外8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。支持这一观点的假设是，I型干扰素在转录上上调子宫内膜中雌激素受体-β(ERbeta)基因的活性，进而调节雌激素受体-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型干扰素单独使用或与抗雌激素联合使用是否具有治疗人类子宫癌的潜力。这项工作将包括研究子宫内膜癌细胞对细胞增殖和凋亡的影响以及对ERa和Erb的调控，确定Erb表达的转录调控的实验，以及比较干扰素对ERa和Erb缺失的小鼠子宫基因表达的影响。当罗森菲尔德博士获得永久职位后，所有这些工作都可以转让。密苏里大学在生殖生物学方面有一个出色的项目，教职员工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课程。该校园提供了丰富的学科组合和协作环境，预计罗森菲尔德博士将继续在这里茁壮成长。