title: Aberrant subcellular immunolocalization of NOTCH-1 activated intracellular domain in feline mammary tumours.
abstract: NOTCH-1 is a transmembrane receptor protein. Ligand proteins expressed on the surface of neighbouring cells bind to the NOTCH-1 extracellular domain by juxtacrine signalling and release the NOTCH intracellular domain (NICD) to alter gene expression. Forty feline mammary lesions (34 malignant and six hyperplastic) were submitted for immunohistochemical analysis of NICD expression using an anti-feline NICD monoclonal antibody. Associations between NICD expression in carcinomas and morphological parameters, as well as overall survival (OS), were investigated. NICD nuclear expression was observed in hyperplastic lesions (100%) while cytoplasmic localization was evident in carcinomas (0% nuclear positive; 87.5% cytoplasmic positive; 12.5% negative). Cytoplasmic NICD localization was statistically associated with carcinomas, while nuclear labelling was associated with hyperplasia. No significant correlation between positive or negative NICD expression and OS or morphological parameters was detected. NOTCH-1 activation, immunohistochemically identified by the NICD active form, appears to play a role in feline mammary carcinoma biology as the majority of tumours express this protein. Nuclear localization is consistent with the established NICD metabolic intranuclear pathway while cytoplasmic accumulation suggests aberrant NOTCH-1 signalling typical of malignant tumour progression.
authors: Veterinary Pathology, School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston CH64 7TE, UK; Department of Animal Pathology, Faculty of Veterinary Medicine, University of Pisa, Viale delle Piagge 2, 56124 Pisa, Italy. Electronic address: l.ressel@liverpool.ac.uk.
authors: L
authors: L
authors: Ressel
authors: Royal (Dick) School of Veterinary Studies and Roslin Institute, Easter Bush Veterinary, Roslin, Midlothian EH25 9RG, UK.
authors: R W
authors: RW
authors: Else
authors: Department of Animal Pathology, Faculty of Veterinary Medicine, University of Pisa, Viale delle Piagge 2, 56124 Pisa, Italy.
authors: A
authors: A
authors: Poli
authors: Royal (Dick) School of Veterinary Studies and Roslin Institute, Easter Bush Veterinary, Roslin, Midlothian EH25 9RG, UK.
authors: D J
authors: DJ
authors: Argyle
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D002371:Cat Diseases / Q000378:metabolism* / Q000473:pathology; D002415:Cats; D005260:Female; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology; D051881:Receptor, Notch1 / Q000378:metabolism*
chemical_list: D051881:Receptor, Notch1
keywords: NOTCH-1; NOTCH-1 intracellular domain; cat; mammary tumours