{"doi":"10.1354/vp.39-3-372","title":"Tumor Suppressor <i>PTEN</i> is Mutated in Canine Osteosarcoma Cell Lines and Tumors","abstract":"<jats:p> Canine osteosarcoma (OS) cell lines contain mutations that directly or indirectly inactivate the tumor suppressor genes p53 and retinoblastoma. Another important tumor suppressor, PTEN, is mutated in many human cancers. To determine whether inactivation of PTEN plays a role in the pathogenesis of canine OS, we studied its expression in canine OS cell lines and tumors. Four of five canine OS cell lines (CO2, CO3, CO5, and CO7) constitutively express high levels of the phosphorylated form of Akt, an indirect indicator of aberrant PTEN expression. PTEN protein is essentially absent from three of these cell lines (CO2, CO5, and CO7), whereas CO3 contains a potentially inactivating amino acid substitution in PTEN at codon 340. Genomic hybridization experiments indicate that CO2, CO5, and CO7 contain large deletions within the PTEN gene. Ten of 15 OS tumors exhibit variable or negative PTEN staining. Evaluation of a PTEN-negative staining tumor by Southern blotting indicates that the PTEN gene is deleted in this tumor. These results indicate that PTEN is mutated or downregulated in a high percentage of canine OS cell lines and tumors and likely plays an important role in the pathogenesis of the disease. </jats:p>","journal":"Veterinary Pathology","year":2002,"id":659895,"datarank":0.692268077526189,"base_score":4.61512051684126,"endowment":4.61512051684126,"self_citation_contribution":0.692268077526189,"citation_network_contribution":0.0,"self_endowment_contribution":0.692268077526189,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":100,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1722575,"name":"T. Forest","orcid":null,"position":1,"is_corresponding":false},{"id":80667,"name":"C. Smith","orcid":"0000-0001-9804-7285","position":2,"is_corresponding":false},{"id":1722574,"name":"R. A. Levine","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tumor Suppressor <i>PTEN</i> is Mutated in Canine Osteosarcoma Cell Lines and Tumors","abstract":"<jats:p> Canine osteosarcoma (OS) cell lines contain mutations that directly or indirectly inactivate the tumor suppressor genes p53 and retinoblastoma. Another important tumor suppressor, PTEN, is mutated in many human cancers. To determine whether inactivation of PTEN plays a role in the pathogenesis of canine OS, we studied its expression in canine OS cell lines and tumors. Four of five canine OS cell lines (CO2, CO3, CO5, and CO7) constitutively express high levels of the phosphorylated form of Akt, an indirect indicator of aberrant PTEN expression. PTEN protein is essentially absent from three of these cell lines (CO2, CO5, and CO7), whereas CO3 contains a potentially inactivating amino acid substitution in PTEN at codon 340. Genomic hybridization experiments indicate that CO2, CO5, and CO7 contain large deletions within the PTEN gene. Ten of 15 OS tumors exhibit variable or negative PTEN staining. Evaluation of a PTEN-negative staining tumor by Southern blotting indicates that the PTEN gene is deleted in this tumor. These results indicate that PTEN is mutated or downregulated in a high percentage of canine OS cell lines and tumors and likely plays an important role in the pathogenesis of the disease. </jats:p>","is_dataset_classified":null,"base_score":4.61512051684126,"endowment":4.61512051684126,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12014501","pmcid":null,"openalex_id":"https://openalex.org/W2151309051","authors":[],"funders":[],"total_grants":0,"fwci":2.1131,"citation_percentile":0.85852234,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":6},{"year":2014,"count":7},{"year":2015,"count":5},{"year":2016,"count":8},{"year":2017,"count":6},{"year":2018,"count":4},{"year":2019,"count":7},{"year":2020,"count":5},{"year":2021,"count":5},{"year":2022,"count":4},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":1}],"oa_status":"closed","license":"https://journals.sagepub.com/page/policies/text-and-data-mining-license","oa_locations":[{"url":"https://journals.sagepub.com/doi/pdf/10.1354/vp.39-3-372","host_type":"publisher"},{"url":"https://journals.sagepub.com/doi/full-xml/10.1354/vp.39-3-372","host_type":"publisher"},{"url":"https://doi.org/10.1354/vp.39-3-372","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12014501","host_type":"repository"}],"fields_of_study":["Infectious Diseases and Mycology","Veterinary Oncology Research","PI3K/AKT/mTOR signaling in cancer","Animals","Blotting, Northern","Blotting, Southern","Blotting, Western","Bone Neoplasms","DNA, Neoplasm","Dog Diseases","Dogs","Female","Gene Expression Regulation, Neoplastic","Immunohistochemistry","Male","Mutation","Nucleic Acid Hybridization","Osteosarcoma","PTEN Phosphohydrolase","Phosphoric Monoester Hydrolases","RNA, Neoplasm","Sequence Analysis, DNA","Tumor Cells, Cultured","Tumor Suppressor Proteins"],"mesh_terms":["Animals","Bone Neoplasms","DNA, Neoplasm","Dog Diseases","Dogs","Female","Immunohistochemistry","Male","Mutation","Nucleic Acid Hybridization","Phosphoric Monoester Hydrolases","RNA, Neoplasm","Osteosarcoma","Tumor Cells, Cultured","Blotting, Southern","Blotting, Northern","Blotting, Western","Gene Expression Regulation, Neoplastic","Sequence Analysis, DNA","Tumor Suppressor Proteins","PTEN Phosphohydrolase"],"keywords":["PTEN","Tumor suppressor gene","Cancer research","Biology","Suppressor","Cell culture","Protein kinase B","Gene","Osteosarcoma","Cell","Molecular biology","PI3K/AKT/mTOR pathway","Signal transduction","Carcinogenesis","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T07:53:25.107204Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}