title: Alterations of C-MYC, NKX3.1, and E-cadherin expression in canine prostate carcinogenesis.
abstract: The dog (canis lupus familiaris) is the only other species besides humans that develop spontaneous prostatic carcinomas (PCa) at a high frequency. The canine model is primarily utilized for the study of the PCa molecular mechanisms and provides a natural animal model for the study of potential therapies. In humans, the PCa frequently exhibits mutations in the C-MYC and a reduced expression of the E-cadherin and NKX3.1 proteins. This study's objective was to evaluate the NKX3.1, C-MYC, and E-cadherin expression in the canine normal prostate, benign prostatic hyperplasia (BPH), proliferative inflammatory atrophy (PIA) and PCa and to verify differences in expression and subcellular localization of these proteins in the prostatic carcinogenesis. A tissue microarray (TMA) slide was constructed, and immunohistochemistry with antibodies raised against C-MYC, NKX3.1, E-cadherin and p63 was performed using the peroxidase and DAB methods. The C-MYC protein expression was elevated in the cytoplasm and nuclei of the canine PCa and PIA compared with the normal prostate (P = 0.004. The NKX3.1 protein expression was reduced in 94.75% of the PCa and 100% of the PIA compared with the normal prostate (P = 0.0022). In fact, the expression of E-cadherin trended towards a decrease in carcinomas when compared to normal prostate and PIA. By immunohistochemistry, more p63-positive basal cells were observed in the PCa and PIA when compared with the normal prostate (P = 0.0002). This study has demonstrated that the carcinogenesis of canine prostatic tissue may be related to basal cell proliferation, the gain of C-MYC function and the loss of NKX3.1 protein expression.
authors.affiliation: Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, Botucatu, Sao Paulo, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Fonseca-Alves
authors.forename: Marcela M P
authors.initials: MM
authors.lastname: Rodrigues
authors.forename: Veridiana M B D
authors.initials: VM
authors.lastname: de Moura
authors.forename: Silvia R
authors.initials: SR
authors.lastname: Rogatto
authors.forename: Renee
authors.initials: R
authors.lastname: Laufer-Amorim
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D004285:Dogs; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D007150:Immunohistochemistry / Q000662:veterinary; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
chemical_list: C081876:CKAP4 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; C489427:MYC protein, human; D008565:Membrane Proteins; C491178:NKX3-1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors
keywords: canine; immunohistochemistry; prostatic carcinoma; protein expression