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: 6950327
• 负责人: Cheryl Susan Rosenfeld
• 金额: $ 15.01万
• 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/6950327
• 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（由申请人提供）：申请人Cheryl Rosenfeld博士拥有D.V.M. （伊利诺伊大学，Urbana-Champaign 1995）和密苏里州的两年解剖病理培训。 然后，她完成了博士学位。在具有丹尼斯·卢巴恩（Dennis Lubahn）博士的动物科学中，卵巢异常和雌激素受体α基因（Erako小鼠）的卵子异常。 她目前是该提案的赞助商的研究助理教授，密苏里州策展人教授，国家科学院成员R. Michael Roberts博士。 罗伯茨博士的兴趣是孕产妇对怀孕的认识，尤其是在大型农场哺乳动物的早期怀孕中通过I型干扰素（IFN）扮演的角色。 罗森菲尔德博士一直在研究绵羊子宫内的IFN受体亚基的结构和分布，作为她的主要项目。 她目前担任兽医微解剖学讲师的25％承诺。 罗森菲尔德（Rosenfeld）博士是七篇被裁判论文的第一作者，还有另外八位的合着者。 她的目标是获得终身教师职位，使她能够在癌症生物学和比较医学方面进行教学和研究。 该提议的基础是I型IFN在子宫内膜中转录上调节雌激素受体β（ERBETA）基因的活性的假设，这反过来又调节了雌激素受体 - α（ERA）的浓度。 这些实验的总体目的是证明这一假设，并确定I型IFN是否单独或与抗雌激素结合使用，具有治疗人子宫癌的潜力。 这项工作将涉及研究对细胞增殖和凋亡的影响以及对子宫内膜癌的细胞的调节或ERA和ERB的影响，确定ERB表达的转录控制的实验，以及微阵列实验，以比较ERA或ERB子宫中IFN对基因表达的效果。 当罗森菲尔德博士担任永久职位时，所有这项工作都是可以转移的。 密苏里大学在生殖生物学方面拥有出色的计划，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方面的工作。 该大学正在制定比较肿瘤学计划。 该校园提供了丰富的学科和协作环境，预计罗森菲尔德博士将继续蓬勃发展。