title: The significance of p53 and retinoblastoma pathways in canine hemangiosarcoma.
abstract: To investigate whether inactivation of the p53 and retinoblastoma (Rb) protein pathways contributes to the development of canine hemangiosarcoma (HSA), we examined immunohistochemically the expression of p53, Rb, phosphorylated Rb (phospho-Rb), p16, and cyclin D1 in 39 spontaneous canine HSAs and 10 hemangiomas. In addition, mutations in the p53 gene were analyzed by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and PCR direct sequencing; furthermore, we quantified cyclin D1 mRNA by semiquantitative real-time reverse transcription-PCR. Positive immunoreactivity for p53 was observed in 17.9% of HSAs. However, mutations were not detected in these cases. The labeling indices for Rb, phospho-Rb, and cyclin D1 were markedly higher in all HSAs than in hemangiomas. Of the 7 cases with cyclin D1-positive immunoreactivity, 4 overexpressed cyclin D1 mRNA (to a level more than 10-fold higher than that of GAPDH mRNA). The p16 protein was clearly detected in all hemangiomas; however, 82% of the neoplastic cells in HSA showed a loss of or low immunoreactivity. These results suggest that alteration of the p16-cyclin D1-Rb pathway, rather than the p53 pathway, may be associated with the pathogenesis of canine HSA.
authors.affiliation: Laboratoriy of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Yonemaru
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sakai
authors.forename: Mami
authors.initials: M
authors.lastname: Murakami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kodama
authors.forename: Takashi
authors.initials: T
authors.lastname: Mori
authors.forename: Tokuma
authors.initials: T
authors.lastname: Yanai
authors.forename: Kohji
authors.initials: K
authors.lastname: Maruo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Masegi
mesh_terms: D000818:Animals; D001483:Base Sequence; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D017931:DNA Primers; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D006394:Hemangiosarcoma / Q000378:metabolism / Q000662:veterinary*; D007150:Immunohistochemistry / Q000662:veterinary; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D016160:Retinoblastoma Protein / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D017422:Sequence Analysis, DNA / Q000662:veterinary; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1