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.
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