Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer

: We previously generated a transgenic model (renamed as PB-Cre4/Ai-Myc) to allow Cre-induced and androgen-independent expression of c-Myc and Luc2 in prostate epithelia. This allows concisely studying castration response and CRPC. However, most PB-Cre4/Ai-Myc mice never developed significant prostate tumors, and knockout of p53 (Year 1) led to tumorigenesis of prostate and epididymis. In Year 2, we performed detailed study on tumor progression in thePB-Cre4/Ai-Myc/p53loxP/loxP mice. They developed unexpected lethal epididymis tumors in 3-5 months. About 30% of them also developed significant prostate tumors by death or the time of euthanization due to epididymis tumor burden. Accordingly, we have proposed and received approval for additional animal studies. We performed early castration on these mice to eliminate concern of epididymis tumors, and performed implantation of testosterone pellets to continue support prostate tumor growth. Our recent data suggest that these surgically operated mice rapidly developed prostate tumors w/o evidence of epididymis tumors, which strongly supports continuing to use our model to study CRPC and chemoresistance of CRPC.