This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zorn, C. S. Articles by Day, M. L. Search for Related Content PubMed PubMed Citation Articles by Zorn, C. S. Articles by Day, M. L.

5-Aza-2'-Deoxycytidine Delays Androgen-Independent Disease and Improves Survival in the Transgenic Adenocarcinoma of the Mouse Prostate Mouse Model of Prostate Cancer

Authors' Affiliations: ¹ Department of Urology, University of Michigan, Ann Arbor, Michigan; ² Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia; ³ Department of Urology, University of Ulm, Ulm, Germany; and ⁴ Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany

Requests for reprints: Mark L. Day, Department of Urology, University of Michigan, 6219 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0944. Phone: 734-763-9968; Fax: 1-734-647-9271; E-mail: mday{at}umich.edu.

Purpose: We have previously shown that 5-aza-2'-deoxycytidine (5-aza) is an effective chemopreventive agent capable of preventing early disease progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The purpose of this study was to determine the effect of 5-aza on preexisting TRAMP prostate cancers and prevention of androgen-independent prostate cancer.

Experimental Design: TRAMP mice with established prostate cancers were treated with 5-aza, castration, castration + 5-aza, or vehicle control (PBS). One cohort of 22 mice per treatment was euthanized after 10 weeks of treatment, whereas a second cohort of 14 mice per group was followed until death to determine survival. Histologic sections of prostate, pelvic lymph nodes, lung, and liver were blinded and analyzed by a certified genitourinary pathologist (K.J.W.).

Results: Combined treatment (castration + 5-aza) provided significant survival benefits over either single treatment (combined versus castration P = 0.029, combined versus 5-aza P = 0.036). At 24 weeks of age, 86% of mice within the PBS cohort exhibited histologic evidence of prostate cancer, whereas only 47% of the combined cohort exhibited malignant disease (P < 0.0001). Additionally, whereas 43% of the PBS treatment group exhibited lymph node metastases, these were only observed in 21% of the combined treatment mice.

Conclusions: This is the first study to examine the effect of 5-aza and combined castration + 5-aza on preexisting prostate cancer in an animal model. Based on these preclinical findings, we suggest that 5-aza treatment may prolong the time to an androgen-independent status and thus survival in a hormone-deprived setting in prostate cancer.

This article has been cited by other articles:

				S. R. Morey Kinney, D. J. Smiraglia, S. R. James, M. T. Moser, B. A. Foster, and A. R. Karpf Stage-Specific Alterations of DNA Methyltransferase Expression, DNA Hypermethylation, and DNA Hypomethylation during Prostate Cancer Progression in the Transgenic Adenocarcinoma of Mouse Prostate Model Mol. Cancer Res., August 1, 2008; 6(8): 1365 - 1374. [Abstract] [Full Text] [PDF]