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A New Proposed Rodent Model of Chemically Induced Prostate Carcinogenesis: Distinct Time-Course Prostate Cancer Progression in the Dorsolateral and Ventral Lobes
Article first published online: 26 APR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 73, Issue 11, pages 1202–1213, August 2013
How to Cite
Gonçalves, B. F., de Campos, S. G.P., Zanetoni, C., Scarano, W. R., Falleiros, L. R., Amorim, R. L., Góes, R. M. and Taboga, S. R. (2013), A New Proposed Rodent Model of Chemically Induced Prostate Carcinogenesis: Distinct Time-Course Prostate Cancer Progression in the Dorsolateral and Ventral Lobes. Prostate, 73: 1202–1213. doi: 10.1002/pros.22669
- Issue published online: 21 JUN 2013
- Article first published online: 26 APR 2013
- Manuscript Accepted: 4 MAR 2013
- Manuscript Received: 30 OCT 2012
- São Paulo Research Foundation—FAPESP. Grant Number: Proc. Nr. 2008/11236-7
- Brazilian National Research and Development Council—CNPq. Grant Number: Proc. Nr. 301596/2011-5
- N-methyl N-nitrosurea;
- prostate cancer;
- alkylating agents
Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes.
Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes.
Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining.
There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Prostate 73: 1202–1213, 2013. © 2013 Wiley Periodicals, Inc.