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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Prostate carcinogenesis induced by N-methyl-N-nitrosourea (mnu) in gerbils: Histopathological diagnosis and potential invasiveness mediated by extracellular matrix components

Texto completo
Autor(es):
Goncalves, Bianca F. [1] ; Zanetoni, Cristiani [2] ; Scarano, Wellerson R. [3] ; Goes, Rejane M. [1] ; Vilamaior, Patricia S. L. [1] ; Taboga, Sebastiao R. [1] ; Campos, Silvana G. P. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Sao Paulo State Univ, Inst Biosci Humanities & Exact Sci, UNESP IIBILCE, Dept Biol, Lab Microscopy & Microanal, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Dept Cell Biol, Inst Biol, BR-13083864 Campinas, SP - Brazil
[3] Sao Paulo State Univ, Dept Morphol, Inst Biosci, BR-18618000 Botucatu, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Experimental and Molecular Pathology; v. 88, n. 1, p. 96-106, FEB 2010.
Citações Web of Science: 9
Resumo

In the present study prostate lesions were induced in gerbils (Meriones unguiculatus) treated with a single N-methyl-N-nitrosourea (MNU) dose; thus, the incidence, latency and histology of these lesions were evaluated. Fibrillar elements of the extracellular matrix associated with microinvasive sites were also investigated. Animals were divided into 5 groups, including 2 control groups: (1) remained untreated; (2) received the corn oil vehicle (vehicle, 0.1 ml/application) and three different tumor induction regimens: (1) received MNU (30 mg/kg) and weekly testosterone (2 mg/kg) (MNU + testosterone); (2) received only MNU (30 mg/kg); (3) received weekly testosterone doses (2 mg/kg). After 3 and 6 months the animals were dissected and the prostates were evaluated morphologically, immunohistochemically and quantitatively. MNU plus androgen contributed to the development of prostatic intraepithelial neoplasia, microinvasive carcinoma and adenocarcinoma in gerbil prostate. However, these lesions occurred earlier in time in groups that received MNU and androgen compared to control animals as they over time also developed to a high extent microinvasive lesions. Cytochemistry and immunohistochemistry showed that these injuries were commonly associated with inflammatory cells whereas the epithelial cells presented proliferative activity. The alpha-methylacyl-CoA racemase (AMACR) expression in prostate cancer cells facilitated diagnosis of gerbil lesions. Testosterone, MNU and MNU + testosterone showed an increased epithelial volume, although the secretory activity was significantly suppressed mainly at neoplastic foci. In the prostatic stroma, reticular fibers increased significantly in MNU, MNU + testosterone and among the lesions found in these groups, while collagen fibers decreased at neoplastic sites. The disruption of the basement membrane was proven at malignant sites by ultrastructural analysis and type IV collagen and laminin degradation. The prostate carcinogenesis mediated by MNU and androgen stimulated the emergence of proliferative lesions in gerbils after short periods and showed the importance of a dynamic remodeling of stromal components for cellular invasiveness. Published by Elsevier Inc. (AU)

Processo FAPESP: 05/04670-4 - Efeitos da supressão androgênica e estrogênica no microambiente prostático do gerbilo velho
Beneficiário:Sebastião Roberto Taboga
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 07/00467-5 - Caracterização de elementos fibrilares do estroma prostático de gerbilos associados a lesões microinvasivas
Beneficiário:Bianca Facchim Gonçalves
Linha de fomento: Bolsas no Brasil - Iniciação Científica