HERSTATIN: A NOVEL CANCER THERAPEUTIC

赫斯汀：一种新型癌症治疗药物

• 批准号: 8357799
• 负责人: Charles T Roberts
• 金额: $ 4.36万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357799
• 关键词: Award; Breast Cancer Cell; C-terminal; Cancer cell line; Cell Line; Coculture Techniques; Funding; Goals; Grant; Growth; In Vitro; Introns; Investigation; Length; Malignant Neoplasms; Malignant neoplasm of prostate; National Center for Research Resources; Peptide Signal Sequences; Plasmid Cloning Vector; Primates; Principal Investigator; Protein Isoforms; Proteins; Proto-Oncogenes; Research; Research Infrastructure; Resources; Source; Subfamily lentivirinae; Therapeutic; United States National Institutes of Health; cost; design; herstatin; in vivo; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project has as its principal goal the characterization of the expression and action of a novel isoform of the Her-2 protooncogene. This isoform, termed herstatin, results from intron retention and the synthesis of a truncated version of Her-2 containing a unique intron-encoded C terminus. The studies supported by this award include assessment of expression and inhibition of growth of prostate and breast cancer cell lines in vitro using transwell co-culture as well as investigation of the activity of C-terminal fragments of the full-length protein. We have most recently investigated the secretion of herstatin from multiple cell lines using both plasmid vector and lentivirus approaches and have employed heterologous signal sequences to enhance secretion. In addition, we have designed a novel version incorporating the intron-encoded domain appended to a TAT protein transduction domain and a KDEL ER retention sequence in order to mimic herstatin function in IN addition, we have designed a novel version incorporating the intron-encoded domain appended to a TAT protein transduction domain and an KDEL ER retention sequence in order to mimic herstatin function in vivo.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该项目的主要目标是表征 Her-2 原癌基因的新型亚型的表达和作用。 这种亚型被称为 Herstatin，是由内含子保留和含有独特内含子编码 C 末端的 Her-2 截短版本合成产生的。 该奖项支持的研究包括使用 Transwell 共培养对前列腺和乳腺癌细胞系的体外表达和生长抑制进行评估，以及对全长蛋白 C 末端片段的活性进行研究。 我们最近使用质粒载体和慢病毒方法研究了多个细胞系中赫他汀的分泌，并采用异源信号序列来增强分泌。此外，我们设计了一种新版本，其中包含附加到 TAT 蛋白转导结构域和 KDEL ER 保留序列的内含子编码结构域，以模拟赫他汀功能。