EVALUATION OF HUMAN PROLACTIN, ITS ANTAGONIST, AND ANTAGONIST-BASED FUSION PROTEINS AS CHEMOPREVENTATIVE AND THERAPEUTIC AGENTS

摘要: Cancer is a collection of diseases with many different manifestations and the second leading cause death in United States. Breast cancer accounts for nearly one third diagnosis women. Prolactin (PRL) functions as lactogen mammary gland differentiation factor. PRL acts an autocrine/paracrine manner within breast tumors which implies may be involved progression. This corroborated by PRLR over-expression cells lines majority patient biopsies. These reasons make attractive targets treatment prevention. Transgenic mice expressing hPRL or G129R, under regulation metallothionein (Mt) promoter, were fed chemical carcinogen, 9,10-Dimethyl-1,2-benzanthracene (DMBA). G129R transgenic exhibited decreased growth rate chemically-induced tumors, while had increased rate. Microarray analysis revealed that showed expression pattern similar to those pregnant mouse, increase various apoptotic markers. Previously, fusion proteins composed antagonist (G129R) anti-tumor domains developed; these included fusions angiogenesis inhibitor (Endostatin), immune system modulator (interleukin-2), cytotoxin (PE38KDEL). The rationale was each protein would target via moiety attack hallmarks common tumor moiety. A novel clinically-relevant model generated surgically removing spontaneous from MMTV-neu monitoring recurrence treating cocktail. Tumor significantly delayed groups treated comparison control group. In conclusion, targeting multiple using combination dual function therapeutics highly effective aggressive mouse model. DEDICATION To only two loves my life, wife, Chrystal, daughter, Elizabeth.