Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer
Technical Report,15 Sep 2013,14 Sep 2017
Baylor College of Medicine Houston United States
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We previously made a PB-Cre4Ai-Myc model for Cre-induced and androgen-independent expression of c-Myc and Luc2 in prostate. This is designed for concisely studying castration response and CRPC. However, most mice never developed significant tumors. Here, we showed that ablation of p53 in this model led to rapid growth of prostate tumors expected based on our hypothesis but with lethal epididymis tumors unexpected. To solve this problem, we performed early castration together with testosterone pellet implantations in these mice. The mice were later divided into two groups, the control continued receiving pellet implantations whereas the castration group underwent a pellet removal procedure. We observed castration-response as evidenced by greatly reduced BLI signal and a lack of AR nuclear localization in the castrated tumors. However, we did not observe significant difference in overall survival and there were large seminal vesicle tumors associated with most prostate tumors in this model. These made it difficult to concisely assess prostate tumor response to castration. We have designed and will use alternative approaches to address this problem in the near future.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research