{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T05:22:47Z","timestamp":1741411367464,"version":"3.38.0"},"reference-count":53,"publisher":"American Veterinary Medical Association (AVMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To investigate the antitumor effect of the chicken anemia virus (CAV) <jats:italic>VP3<\/jats:italic> gene in canine mammary tumor (CMT) cells.<\/jats:p>\n<jats:p><jats:bold>Sample Populations<\/jats:bold>\u2014Established primary canine cell lines that originated from epithelial cells of resected CMTs and nonneoplastic mammary gland epithelial (MGE) cells.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Expression vectors and lentiviral vectors encoding the <jats:italic>VP3<\/jats:italic> gene from a Taiwan-Ilan isolate of CAV were used to deliver the <jats:italic>VP3<\/jats:italic> gene into CMT cells and nonneoplastic MGE cells. Ectopic gene expression and the pro-apoptotic effect of the <jats:italic>VP3<\/jats:italic> gene on CMT and nonneoplastic MGE cells by either transfection or viral infection were evaluated via immunofluorescence microscopy, western blot analysis, and terminal deoxynucleotidyl transferase\u2013mediated dUTP nick-end labeling analysis.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Overexpression of the enhanced green fluorescent protein\u2013VP3 fusion protein was detected predominantly in the nuclei of CMT cells. In contrast, the VP3 protein was localized to the cytoplasm of nonneoplastic MGE cells. Among the fusion protein\u2013expressing CMT cells, most underwent characteristic changes of apoptosis, whereas apoptosis was not detected in fusion protein\u2013expressing, nonneoplastic MGE cells. Induction of apoptosis by <jats:italic>VP3<\/jats:italic> gene overexpression in CMT cells was associated with the caspase-9\u2013, but not the caspase-8\u2013, mediated apoptosis pathway.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014These data indicate that the <jats:italic>VP3<\/jats:italic> gene of the CAV induces apoptosis in malignant CMT cells, but not in nonneoplastic canine MGE cells. On the basis of such tumor cell\u2013specific killing, the <jats:italic>VP3<\/jats:italic> gene may be a promising agent for the treatment of malignant mammary gland tumors in dogs.<\/jats:p>","DOI":"10.2460\/ajvr.68.4.411","type":"journal-article","created":{"date-parts":[[2007,4,1]],"date-time":"2007-04-01T13:34:44Z","timestamp":1175434484000},"page":"411-422","source":"Crossref","is-referenced-by-count":4,"title":["Effect of the VP3 gene of chicken anemia virus on canine mammary tumor cells"],"prefix":"10.2460","volume":"68","author":[{"given":"Jih-Jong","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poshen 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Pathol","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1177\/030098588602300613","article-title":"Mammary tumors in a colony of beagle dogs","volume":"23","author":"Moulton","year":"1986"},{"key":"ref2","series-title":"J Natl Cancer Inst","first-page":"1249","article-title":"Factors influencing canine mammary cancer development and postsurgical survival","volume":"43","author":"Schneider","year":"1969"},{"key":"ref3","series-title":"Cancer Metastasis Rev","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/BF00046339","article-title":"Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment","volume":"9","author":"MacEwen","year":"1990"},{"key":"ref4","series-title":"J Mammary Gland Biol Neoplasia","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/BF02096299","article-title":"The mammary gland: a unique organ for the study of development and tumorigenesis","volume":"1","author":"Medina","year":"1996"},{"key":"ref5","series-title":"Endocr Relat Cancer","first-page":"257","article-title":"Apoptosis in mammary gland and cancer","volume":"7","author":"Kumar","year":"2000"},{"key":"ref6","series-title":"Science","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1126\/science.7878464","article-title":"Apoptosis in the pathogenesis and treatment of disease","volume":"267","author":"Thompson","year":"1995"},{"key":"ref7","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"14602","DOI":"10.1074\/jbc.M309008200","article-title":"Autocrine\/paracrine secreted frizzled-related protein 2 induces cellular resistance to apoptosis: a possible mechanism of mammary tumorigenesis","volume":"279","author":"Lee","year":"2004"},{"key":"ref8","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1073\/pnas.93.6.2239","article-title":"The molecular biology of apoptosis","volume":"93","author":"Vaux","year":"1996"},{"key":"ref9","series-title":"J Gen Virol","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1099\/0022-1317-79-8-1833","article-title":"Viruses and apoptosis","volume":"79","author":"O'Brien","year":"1998"},{"key":"ref10","series-title":"Dev Comp Immunol","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0145-305X(99)00076-2","article-title":"Immunopathogenesis of chicken anemia virus infection","volume":"24","author":"Adair","year":"2000"},{"key":"ref11","series-title":"J Gen Virol","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1099\/0022-1317-71-4-819","article-title":"Purification and biochemical characterization of chicken anemia agent","volume":"71","author":"Todd","year":"1990"},{"key":"ref12","series-title":"Gene","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0378-1119(92)90198-X","article-title":"Transcription of the chicken anemia virus (CAV) genome and synthesis of its 53-kDa protein","volume":"118","author":"Noteborn","year":"1992"},{"key":"ref13","series-title":"J Virol","doi-asserted-by":"publisher","first-page":"7383","DOI":"10.1128\/jvi.66.12.7383-7388.1992","article-title":"Chicken anemia virus causes apoptosis of thymocytes after in vivo infection and of cell lines after in vitro infection","volume":"66","author":"Jeurissen","year":"1992"},{"key":"ref14","series-title":"Avian Dis","doi-asserted-by":"publisher","first-page":"168","DOI":"10.2307\/1592590","article-title":"Recommended storage and resuscitation conditions for the MDCC-MSB1 cell line","volume":"42","author":"Coombes","year":"1998"},{"key":"ref15","series-title":"Vaccine","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/0264-410X(94)00034-K","article-title":"Immunogenic and protective properties of chicken anaemia virus proteins expressed by baculovirus","volume":"13","author":"Koch","year":"1995"},{"key":"ref16","series-title":"J Chin Soc Vet Sci","first-page":"74","article-title":"A Taiwanese isolate of chicken anemia virus induces apoptosis in the in vitro culture cells","volume":"27","author":"Chiu","year":"2001"},{"key":"ref17","series-title":"J Virol","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1128\/jvi.68.1.346-351.1994","article-title":"A single chicken anemia virus protein induces apoptosis","volume":"68","author":"Noteborn","year":"1994"},{"key":"ref18","series-title":"Mutat Res","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/S0027-5107(98)00016-5","article-title":"VP3 specifically causes apoptosis in tumor cells and after UV-treatment in untransformed cells from cancer-prone individuals: a review","volume":"400","author":"Noteborn","year":"1998"},{"key":"ref19","series-title":"Vet Microbiol","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.vetmic.2003.10.003","article-title":"Chicken anemia virus induced apoptosis: underlying molecular mechanisms","volume":"98","author":"Noteborn","year":"2004"},{"key":"ref20","series-title":"J Cell Sci","doi-asserted-by":"publisher","first-page":"4485","DOI":"10.1242\/jcs.02580","article-title":"Cancer-specific toxicity of VP3 is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a Nur77-dependent pathway","volume":"118","author":"Maddika","year":"2005"},{"key":"ref21","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"5843","DOI":"10.1073\/pnas.94.11.5843","article-title":"VP3 induces apoptosis in human transformed and malignant cells but not in normal cells","volume":"94","author":"Danen-Van Oorschot","year":"1997"},{"key":"ref22","series-title":"In Vitro Cell Dev Biol Anim","first-page":"2221","article-title":"Expression of secreted frizzled-related protein 2 in a primary canine mammary tumor cell line: a candidate tumor marker for mammary tumor cells","volume":"39","author":"Lee","year":"2003"},{"key":"ref23","series-title":"J Chin Soc Vet Sci","first-page":"182","article-title":"Molecular cloning and sequence analysis of VP3 gene of chicken anemia virus Taiwanese Ilan strain","volume":"26","author":"Yang","year":"2000"},{"key":"ref24","series-title":"Nat Med","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/nm0398-354","article-title":"Efficient transduction of nondividing human cells by feline immunodeficiency virus lentiviral vectors","volume":"4","author":"Poeschla","year":"1998"},{"key":"ref25","series-title":"J Mol Med","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s00109-003-0486-z","article-title":"The tumor-selective viral protein VP3 effectively kills human biliary tract cancer cells","volume":"82","author":"Pietersen","year":"2004"},{"key":"ref26","series-title":"Avian Dis","first-page":"73","article-title":"Genetic characterization of chicken anemia virus from commercial broiler chickens in Alabama","volume":"45","author":"van Santen","year":"2001"},{"key":"ref27","series-title":"Cancer Res","first-page":"486","article-title":"VP3, a protein derived from chicken anemia virus, induces p53, a protein derived from chicken anemia virus, induces p53-independent apoptosis in human osteosarcoma cells","volume":"55","author":"Zhuang","year":"1995"},{"key":"ref28","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"27729","DOI":"10.1074\/jbc.M303114200","article-title":"Importance of nuclear localization of VP3 for tumor-specific induction of apoptosis","volume":"278","author":"Danen-Van Oorschot","year":"2003"},{"key":"ref29","series-title":"Cancer Biol Ther","doi-asserted-by":"publisher","first-page":"10","DOI":"10.4161\/cbt.5.1.2400","article-title":"Cancer-selective therapy of the future. Apoptin and its mechanism of action","volume":"5","author":"Maddika","year":"2006"},{"key":"ref30","series-title":"J Virol","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1128\/JVI.79.2.1339-1341.2005","article-title":"A tumor specific nuclear targeting signal within chicken anemia virus VP3\/apoptin","volume":"79","author":"Poon","year":"2005"},{"key":"ref31","series-title":"Cancer Res","doi-asserted-by":"publisher","first-page":"7059","DOI":"10.1158\/0008-5472.CAN-05-1370","article-title":"Apoptin nuclear accumulation is modulated by a CRM1-recognized nuclear export signal that is active in normal but not in tumor cells","volume":"65","author":"Poon","year":"2005"},{"key":"ref32","series-title":"J Virol","doi-asserted-by":"publisher","first-page":"7535","DOI":"10.1128\/JVI.02741-05","article-title":"Apoptin nucleocytoplasmic shuttling is required for cell type-specific localization, apoptosis, and recruitment of the anaphase-promoting complex\/cyclosome to PML bodies","volume":"80","author":"Heilman","year":"2006"},{"key":"ref33","series-title":"J Natl Cancer Inst","first-page":"307","article-title":"Survey of animal neoplasms in Alameda and Contra Costa counties, California. II. Cancer morbidity in dogs and cats from Alameda County","volume":"40","author":"Dorn","year":"1968"},{"key":"ref34","series-title":"Clin Tech Small Anim Pract","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1053\/svms.2003.36625","article-title":"Principles of treatment for mammary gland tumors","volume":"18","author":"Novosad","year":"2003"},{"key":"ref35","series-title":"J Small Anim Pract","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1111\/j.1748-5827.2002.tb00066.x","article-title":"Canine neoplasia in the UK: estimates of incidence rates from a population of insured dogs","volume":"43","author":"Dobson","year":"2002"},{"key":"ref36","series-title":"Vet Pathol","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1177\/030098588302000201","article-title":"Canine mammary epithelial neoplasms: biologic implications of morphologic characteristics assessed in 232 dogs","volume":"20","author":"Gilbertson","year":"1983"},{"key":"ref37","series-title":"Vet Pathol","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1354\/vp.36-5-423","article-title":"Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles","volume":"36","author":"Benjamin","year":"1999"},{"issue":"(1 suppl)","key":"ref38","series-title":"J Invest Dermatol","doi-asserted-by":"publisher","first-page":"104s","DOI":"10.1111\/1523-1747.ep12540811","article-title":"Intermediate filaments as histologic markers: an overview","volume":"81","author":"Osborn","year":"1983"},{"key":"ref39","series-title":"Breast Cancer Res Treat","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1023\/B:BREA.0000018412.83348.ff","article-title":"Secreted frizzled-related protein 2 (SFRP2) is highly expressed in canine mammary gland tumors but not in normal mammary glands","volume":"84","author":"Lee","year":"2004"},{"key":"ref40","series-title":"Cancer Gene Ther","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/sj.cgt.7700397","article-title":"Gene therapy with apoptin induces regression of xenografted human hepatomas","volume":"9","author":"van der Eb","year":"2002"},{"key":"ref41","series-title":"Genes Dev","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1101\/gad.1198404","article-title":"The viral protein VP3 associates with the anaphase-promoting complex to induce G2\/M arrest and apoptosis in the absence of p53","volume":"18","author":"Teodoro","year":"2004"},{"key":"ref42","series-title":"Oncogene","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/sj.onc.1207224","article-title":"TAT-VP3 is efficiently delivered and induces apoptosis in cancer cells","volume":"23","author":"Guelen","year":"2004"},{"key":"ref43","series-title":"Hum Gene Ther","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1089\/hum.2005.16.937","article-title":"Phase I study of liposome-DNA complexes encoding the interleukin-2 gene in dogs with osteosarcoma lung metastases","volume":"16","author":"Dow","year":"2005"},{"key":"ref44","series-title":"Cancer Immunol Immunother","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s00262-003-0387-6","article-title":"Intralesional lipid-complexed cytokine\/superantigen immunogene therapy for spontaneous canine tumors","volume":"52","author":"Thamm","year":"2003"},{"key":"ref45","series-title":"Cancer Immunol Immunother","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s002620050595","article-title":"Effective cancer therapy with a single injection of interleukin-2 at the site of the tumour","volume":"48","author":"Otter","year":"1999"},{"key":"ref46","series-title":"Cancer Immunol Immunother","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s00262-004-0627-4","article-title":"Local interleukin 2 therapy is most effective against cancer when injected intratumourally","volume":"54","author":"Jacob","year":"2005"},{"key":"ref47","series-title":"Cancer Immunol Immunother","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s002620000132","article-title":"Synergy between interleukin-2 and prothymosin alpha for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas","volume":"49","author":"Voutsas","year":"2000"},{"key":"ref48","series-title":"Clin Cancer Res","first-page":"1196","article-title":"A novel design of targeted endocrine and cytokine therapy for breast cancer","volume":"8","author":"Zhang","year":"2002"},{"key":"ref49","series-title":"Eur J Immunol","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.1002\/1521-4141(2001010)31:10<3016::AID-IMMU3016>3.0.CO;2-J","article-title":"Interleukin-2 enhances the natural killer cell response to Herceptincoated Her2\/neu-positive breast cancer cells","volume":"31","author":"Carsen","year":"2001"},{"key":"ref50","series-title":"J Immunother","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1097\/00002371-200009000-00007","article-title":"Recombinant vaccinia virus encoding human MUC1 and IL2 as immunotherapy in patients with breast cancer","volume":"23","author":"Scholl","year":"2000"},{"key":"ref51","series-title":"Gene Ther","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/sj.gt.3300833","article-title":"Adenovector-mediated gene delivery of interleukin-2 in metastatic breast cancer and melanoma: results of a phase 1 clinical trial","volume":"6","author":"Stewart","year":"1999"},{"key":"ref52","series-title":"Cancer Immunol Immunother","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s002620050516","volume":"47","author":"Tonini","year":"1998"},{"issue":"(46 suppl)","key":"ref53","series-title":"Hepatogastroenterology","first-page":"1280","article-title":"Local low-dose IL-2 therapy","volume":"1","author":"Den Otter","year":"1999"}],"container-title":["American 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