{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:16:41Z","timestamp":1778771801440,"version":"3.51.4"},"reference-count":30,"publisher":"American Veterinary Medical Association (AVMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"s001\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To examine effects of a common mutation (2-base insertion in exon 5) of the <jats:italic>TP53<\/jats:italic> gene on biological function of p53 protein in canine histiocytic sarcoma cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s002\">\n<jats:title>SAMPLE<\/jats:title>\n<jats:p>Canine histiocytic tumor cell lines DH82 with deletion of <jats:italic>TP53<\/jats:italic> and CHS-3 with the wild-type <jats:italic>TP53<\/jats:italic> and canine wild-type and mutant <jats:italic>TP53<\/jats:italic> fragments.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s003\">\n<jats:title>PROCEDURES<\/jats:title>\n<jats:p>Wild-type or mutant <jats:italic>TP53<\/jats:italic> with a polyprotein peptide tag at the N-terminus was transduced into DH82 and CHS-3 cells. Expression of p53 protein, changes in function as a transcription factor, and susceptibility to doxorubicin and nimustine were compared.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s004\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Transduced p53 protein was detected in wild-type <jats:italic>TP53<\/jats:italic>\u2013transduced DH82 and CHS-3 cells, whereas expression was not detected in mutant <jats:italic>TP53<\/jats:italic>\u2013transduced cells. There were significant increases in expression of target genes of p53 protein, including <jats:italic>p21<\/jats:italic> and <jats:italic>MDM2<\/jats:italic>, in wild-type <jats:italic>TP53<\/jats:italic>\u2013transduced cells, compared with results for native and mock-transfected cells, but not in mutant <jats:italic>TP53<\/jats:italic>\u2013transduced cells. There was no significant difference in drug susceptibilities among native and derivative cells of CHS-3. However, cell viabilities of wild-type <jats:italic>TP53<\/jats:italic>\u2013transduced DH82 cells incubated with doxorubicin were significantly lower than viabilities of native, mock-transfected, and AT insertion mutation\u2013<jats:italic>TP53<\/jats:italic>\u2013transduced DH82 cells; susceptibility to nimustine did not differ significantly among cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s005\">\n<jats:title>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:title>\n<jats:p>Expression of p53 protein and its function as a transcription factor were lost after addition of a 2-base insertion in the <jats:italic>TP53<\/jats:italic> gene in canine histiocytic tumor cells. Additional studies are needed to investigate the clinical relevance of this mutation in histiocytic sarcomas of dogs.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.80.7.680","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T13:02:40Z","timestamp":1561640560000},"page":"680-688","source":"Crossref","is-referenced-by-count":2,"title":["Effect of a two-base insertion mutation of the TP53 gene on expression of p53 protein in canine histiocytic sarcoma cells"],"prefix":"10.2460","volume":"80","author":[{"given":"Hajime","family":"Asada","sequence":"first","affiliation":[{"name":"1Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113\u20138657, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Tomiyasu","sequence":"additional","affiliation":[{"name":"1Department of Veterinary Internal Medicine, Graduate School of Agricultural and 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