A New Proposed Rodent Model of Chemically Induced Prostate Carcinogenesis: Distinct Time-Course Prostate Cancer Progression in the Dorsolateral and Ventral Lobes

Autor(es)

Goncalves, Bianca F. ^[1] ; de Campos, Silvana G. P. ^[2] ; Zanetoni, Cristiani ^[2] ; Scarano, Wellerson R. ^[3] ; Falleiros, Jr., Luiz R. ^[2] ; Amorim, Renee L. ^[4] ; Goes, Rejane M. ^[2] ; Taboga, Sebastiao R. ^[2]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Cell Biol, Campinas, SP - Brazil

^[2] So Paulo State Univ UNESP, Inst Biosci Humanities & Exact Sci IBILCE, Lab Microscopy & Microanal, Dept Biol, So Jos Do Rio Preto - Brazil

^[3] So Paulo State Univ UNESP, Inst Biosci, Dept Morphol, Botucatu, SP - Brazil

^[4] So Paulo State Univ UNESP, Coll Vet Med & Anim Sci FMVZ, Dept Vet Clin Sci, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROSTATE; v. 73, n. 11, p. 1202-1213, AUG 2013.
• Citações Web of Science: 17

Resumo

BACKGROUND. 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. METHODS. 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 alpha-actin, p63, MGMT, and E-cadherin) were studied in both lobes. RESULTS. 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. CONCLUSIONS. 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. (C) 2013 Wiley Periodicals, Inc. (AU)

• Processo FAPESP: 08/11236-7 - Carcinogênese prostática quimicamente induzida por N-metil N-nitrosuréia (MNU) em gerbilos da Mongólia: associação com promotores esteroides ou dieta hiperlipídica
• Beneficiário: Bianca Facchim Gonçalves
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto