Deregulation of E-cadherin, beta-catenin, APC and Caveolin-1 expression occurs in canine prostate cancer and metastatic processes

Autor(es)

Kobayashi, Priscila E. ^[1] ; Fonseca-Alves, Carlos E. ^[1] ; Rivera-Calderon, Luis G. ^[2] ; Carvalho, Marcio ^[1] ; Kuasne, Hellen ^[3] ; Rogatto, Silvia R. ^{[4, 5]} ; Laufer-Arnorim, Renee ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ Unesp, Dept Vet Clin, Sch Vet Med & Anim Sci, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Agr & Vet Sci, Dept Vet Pathol, Jaboticabal, SP - Brazil

^[3] AC Camargo Hosp, Int Ctr Res CIPE, Liberdade, SP - Brazil

^[4] Univ Southern Denmark, Vejle Hosp, Dept Clin Genet, Odense - Denmark

^[5] Univ Southern Denmark, Inst Reg Hlth, Odense - Denmark

• Tipo de documento: Artigo Científico
• Fonte: Research in Veterinary Science; v. 118, p. 254-261, JUN 2018.
• Citações Web of Science: 6

Resumo

Prostate cancer is a heterogeneous disease with high levels of clinical and gene heterogeneity, consequently offering several targets for therapy. Dogs with naturally occurring prostate cancer are useful models for molecular investigations and studying new treatment efficacy. Three genes and proteins associated with the WNT pathway (beta-catenin, APC and E-cadherin) and Caveolin-1 (CAV-1) were evaluated in canine pre-neoplastic proliferative inflammatory atrophy (PIA), prostate cancer and metastatic disease. The APC gene methylation status was also investigated. As in human prostate cancer, cytoplasmic and nuclear beta-catenin, which are fundamental for activating the canonical WNT pathway, were found in canine prostate cancer and metastasis. Membranous E-cadherin was also lost in these lesions, allowing cellular migration to the stroma and nuclear localization of beta-catenin. In contrast to human prostate tumours, no APC downregulation or hypermethylation was found in canine prostate cancer. The CA V-1 gene and protein overexpression were found in canine prostate cancer, and as in humans, the highest levels were found in Gleason scores >= 8. In conclusion, as with human prostate cancer, beta-catenin and E-cadherin in the WNT pathway, as well as Caveolin-1, are molecular drivers in canine prostate cancer. These findings provide additional evidence that dogs are useful models for studying new therapeutic targets in prostate cancer. (AU)

• Processo FAPESP: 12/16068-0 - Avaliação epigenética dos genes NKX3.1 e CDH1 e expressão do c-myc, NKX3.1 e caderina-E por imunoistoquímica em microarranjo de tecido (TMA) de lesões pré-neoplásicas e neoplásicas na próstata de cães
• Beneficiário: Renee Laufer Amorim
• Modalidade de apoio: Auxílio à Pesquisa - Regular