HERSTATIN: A NOVEL CANCER THERAPEUTIC

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目的主要目标是表征Her-2原癌基因的一种新亚型的表达和作用。 这种异构体，称为herstatin，结果从内含子保留和合成的截短版本的Her-2含有一个独特的内含子编码的C末端。 该奖项支持的研究包括使用transwell共培养评估体外前列腺癌和乳腺癌细胞系的表达和生长抑制，以及全长蛋白质C末端片段的活性研究。 我们最近研究了使用质粒载体和慢病毒方法从多个细胞系中分泌herstatin，并采用异源信号序列来增强分泌。此外，我们设计了一种新的形式，其并入了附加到达特蛋白转导结构域的内含子编码结构域和KDEL ER保留序列，以模拟IN中的herstatin功能。此外，我们设计了一种新的形式，其并入了附加到达特蛋白转导结构域的内含子编码结构域和KDEL ER保留序列，以模拟体内herstatin功能。

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.