HERSTATIN: A NOVEL CANCER THERAPEUTIC

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该项目的主要目标是表征一种新的HER-2原癌基因亚型的表达和作用。这种被称为Herstatin的异构体是内含子保留和含有唯一内含子编码的C末端的HER-2的截短版本合成的结果。该奖项支持的研究包括使用Transwell共培养评估前列腺癌和乳腺癌细胞株的体外表达和抑制生长，以及调查全长蛋白质的C末端片段的活性。最近，我们利用质粒载体和慢病毒方法研究了多个细胞系中Herstatin的分泌，并使用了异源信号序列来促进分泌。此外，我们还设计了一个新的版本，将内含子编码的结构域附加到TAT蛋白转导结构域和KDEL ER保留序列中，以模拟Herstatin的功能。此外，我们还设计了一个新的版本，将内含子编码的结构域附加到TAT蛋白转导结构域和KDEL ER保留序列中，以在体内模拟Herstatin的功能。

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.