Alterations of C-MYC, NKX3.1, and E-cadherin expression in canine prostate carcinogenesis

The dog (canis lupus familiaris) is the only other species besides humans thatdevelop spontaneous prostatic carcinomas (PCa) at a high frequency. The canine model is pri-marily utili zed for the study of the PCa molecular mechanisms and provides a natural animalmodel for the study of potential thera...

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Bibliographic Details
Published in:Microscopy Research and Technique
Main Authors: Fonseca-Alves, Carlos Eduardo, Rodrigues, Marcela Marcondes Pinto, Moura, Veridiana Maria Brianezi Dignani de, Rogatto, Silvia Regina, Laufer-Amorim, Renee
Other Authors: Universidade Estadual Paulista (UNESP)
Format: Other/Unknown Material
Language:English
Published: 2016
Subjects:
Online Access:http://acervodigital.unesp.br/handle/11449/140550
http://hdl.handle.net/11449/140550
https://doi.org/10.1002/jemt.22292
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Summary:The dog (canis lupus familiaris) is the only other species besides humans thatdevelop spontaneous prostatic carcinomas (PCa) at a high frequency. The canine model is pri-marily utili zed for the study of the PCa molecular mechanisms and provides a natural animalmodel for the study of potential therapies. In humans, the PCa frequently exhibits mutations inthe C-MYC and a reduced expression of the E-cadherin and NKX3.1 proteins. This study’s objec-tivewastoevaluatetheNKX3.1,C-MYC,andE-cadherinexpressioninthecaninenormalpros-tate, benign p rostatic hyperplasia (BPH), proliferative inflammatory atrophy (PIA) and PCa andto verify differences in expression and subcellula r localiz ation of these proteins in the prostaticcarcinogenesis. A tissue microarray (TMA) slide was constructed, and immunohistochemistrywith antibodies raised against C-MYC, NKX3.1, E-cadherin and p63 was performed using theperoxidase and DAB methods. The C -MYC protein expression was elevated in the cytoplasm andnuclei of t he canine PCa a nd PIA compared with the normal prostate (P 5 0.004. The NKX3.1protein expression was reduced in 94.75% o f the PCa and 100% of the PIA compared with thenormal prostate (P 5 0.0022). In fact, t he expression of E-c adherin trended towards a decrease incarcinomas when compared t o normal p rostate and PIA. By immunohistochemistry, more p63-positive basal cells were observed in the P Ca and PIA when compared with the normal prostate(P 5 0.0002). T his study has demonst rated that the carcinogenesis of canine prostatic tissue maybe related to basal cel l proliferation, the gain of C-MYC fu nc tion and the loss of NKX3.1 pr oteinexpression. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)