A Novel Mechanism of Androgen Receptor Action
Final rept. 15 Dec 2004-14 Dec 2008
OREGON HEALTH AND SCIENCES UNIV PORTLAND
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This revised project had as its goal the characterization of a novel alternative product of the Her-2neuerbB2 protooncogene derived from intron retention. The product of this splicing mechanism, termed herstatin, is a secreted protein comprised of the N terminus of the Her-2 receptor tyrosine kinase and a unique, intron-encoded C terminus that allows binding to the other members of the EGFRerbB family. This binding down-regulates erbB expression and inhibits EGF family signaling and cell proliferation. During this project, we demonstrated that herstatin also down-regulates the IGF-I receptor IGF-IR and modulates IGF signal transduction and action, establishing that herstatin is a novel bifunctional inhibitor of erbB and IGF-IR signaling. We also have shown that herstatin is expressed in prostate tissue and prostate cancers of various stages, and can inhibit CaP cell proliferation. We have also demonstrated differential effects of plasmid vs lentivirus-expressed herstatin that will be of relevance to the development of herstatin as a potential therapeutic approach for CaP.
- Medicine and Medical Research