PMID- 17409643 OWN - NLM STAT- MEDLINE DCOM- 20070718 LR - 20190606 IS - 0916-7250 (Print) IS - 0916-7250 (Linking) VI - 69 IP - 3 DP - 2007 Mar TI - The significance of p53 and retinoblastoma pathways in canine hemangiosarcoma. PG - 271-8 AB - 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. FAU - Yonemaru, Kayoko AU - Yonemaru K AD - Laboratoriy of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Japan. FAU - Sakai, Hiroki AU - Sakai H FAU - Murakami, Mami AU - Murakami M FAU - Kodama, Atsushi AU - Kodama A FAU - Mori, Takashi AU - Mori T FAU - Yanai, Tokuma AU - Yanai T FAU - Maruo, Kohji AU - Maruo K FAU - Masegi, Toshiaki AU - Masegi T LA - eng PT - Comparative Study PT - Journal Article PL - Japan TA - J Vet Med Sci JT - The Journal of veterinary medical science JID - 9105360 RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (DNA Primers) RN - 0 (Retinoblastoma Protein) RN - 0 (Tumor Suppressor Protein p53) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Animals MH - Base Sequence MH - Cyclin D1/genetics/metabolism MH - Cyclin-Dependent Kinase Inhibitor p16/metabolism MH - DNA Primers MH - Dog Diseases/*metabolism MH - Dogs MH - Hemangiosarcoma/metabolism/*veterinary MH - Immunohistochemistry/veterinary MH - Molecular Sequence Data MH - Polymorphism, Single-Stranded Conformational MH - Retinoblastoma Protein/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction/veterinary MH - Sequence Analysis, DNA/veterinary MH - Signal Transduction/*physiology MH - Tumor Suppressor Protein p53/genetics/*metabolism EDAT- 2007/04/06 09:00 MHDA- 2007/07/19 09:00 CRDT- 2007/04/06 09:00 PHST- 2007/04/06 09:00 [pubmed] PHST- 2007/07/19 09:00 [medline] PHST- 2007/04/06 09:00 [entrez] AID - JST.JSTAGE/jvms/69.271 [pii] AID - 10.1292/jvms.69.271 [doi] PST - ppublish SO - J Vet Med Sci. 2007 Mar;69(3):271-8. doi: 10.1292/jvms.69.271.