{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T22:29:20Z","timestamp":1770071360971,"version":"3.49.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> JC virus (JCV) infects 80\u201390% of the population and results in progressive multifocal leukoencephalopathy upon immunodeficiency. The study aimed to pathologically clarify the oncogenic roles of T antigen in human breast cancers.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Breast cancer, dysplasia, and normal tissues were examined for <jats:italic>T antigen<\/jats:italic> of JCV by nested and real-time PCR. The positive rate or copy number of T antigen was compared with clinicopathological parameters of breast cancer. JCV existence was morphologically detected by immunohistochemistry and <jats:italic>in situ<\/jats:italic> PCR. T antigen was examined by Western blot using frozen samples of breast cancer and paired normal tissues.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> According to nested PCR, the positive rate of breast ductal or lobular carcinoma was lower than that of normal tissue (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). T antigen existence was negatively correlated with E-cadherin expression and triple-negative breast cancer (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), but positively correlated with lymph node metastasis and estrogen receptor and progestogen receptor expression (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Quantitative PCR showed that JCV copies were gradually decreased from normal, dysplasia to cancer tissues (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). JCV T antigen copy number was lower in ductal adenocarcinoma than in normal tissue (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), in line with in situ PCR and immunohistochemistry. JCV copies were negatively correlated with tumor size and E-cadherin expression (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), but positively correlated with G grading of breast cancer (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Western blot also indicated weaker T antigen expression in breast cancer than normal tissues (<jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> JCV T antigen might play an important role in breast carcinogenesis. It can be employed as a molecular marker for the differentiation and aggressive behaviors of breast cancer.<\/jats:p>","DOI":"10.3389\/fmolb.2021.687444","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T09:56:34Z","timestamp":1628762194000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["The Oncogenic Roles of JC Virus T Antigen in Breast Carcinogenesis"],"prefix":"10.3389","volume":"8","author":[{"given":"Hua-chuan","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"E","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng-guo","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"6236","DOI":"10.3390\/ijms21176236","article-title":"The Role of the JC Virus in central Nervous System Tumorigenesis","volume":"21","author":"Ahye","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e39842","DOI":"10.1371\/journal.pone.0039842","article-title":"Exploring the Prevalence of Ten Polyomaviruses and Two Herpes Viruses in Breast Cancer","volume":"7","author":"Antonsson","year":"2012","journal-title":"PLoS One"},{"key":"B3","first-page":"189","article-title":"High Frequency of JCV DNA Detection in Prostate Cancer Tissues","volume":"12","author":"Anzivino","year":"2015","journal-title":"Cancer Genomics Proteomics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1515\/hsz-2016-0345","article-title":"The Biology of JC Polyomavirus","volume":"398","author":"Assetta","year":"2017","journal-title":"Biol. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1080\/15384101.2015.1042631","article-title":"Degradation of Polyomavirus JC T-Antigen by Stress Involves the LIP Isoform of C\/EBP","volume":"14","author":"Bellizzi","year":"2015","journal-title":"Cell Cycle"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.3390\/v12101190","article-title":"Phosphoinositide 3\u2032-Kinase \u03b3 Facilitates Polyomavirus Infection","volume":"12","author":"Clark","year":"2020","journal-title":"Viruses"},{"key":"B7","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/978-3-030-20301-6_2","article-title":"Epidemiology of Breast Cancer in Women","volume":"1152","author":"Coughlin","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3390\/v13020162","article-title":"Induction of Brain Tumors by the Archetype Strain of Human Neurotropic JCPyV in a Transgenic Mouse Model","volume":"13","author":"Del Valle","year":"2021","journal-title":"Viruses"},{"key":"B9","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1002\/cncr.20806","article-title":"Detection of JC Virus DNA Sequences and Expression of Viral T Antigen and Agnoprotein in Esophageal Carcinoma","volume":"103","author":"Del Valle","year":"2005","journal-title":"Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13027-017-0122-0","article-title":"Review on the Role of the Human Polyomavirus JC in the Development of Tumors","volume":"12","author":"Delbue","year":"2017","journal-title":"Infect. Agent Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"130","DOI":"10.18632\/genesandcancer.174","article-title":"Viral Tumor Antigen Expression Is No Longer Required in Radiation-Resistant Subpopulation of JCV Induced Mouse Medulloblastoma Cells","volume":"9","author":"Donadoni","year":"2018","journal-title":"Genes Cancer"},{"key":"B12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s13104-019-4178-3","article-title":"No Detection of EBV, BKV and JCV in Breast Cancer Tissue Samples in Iran","volume":"12","author":"Dowran","year":"2019","journal-title":"BMC Res. Notes"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1756286421998915","DOI":"10.1177\/1756286421998915","article-title":"High Rates of JCV Seroconversion in a Large International Cohort of Natalizumab-Treated Patients","volume":"14","author":"Dwyer","year":"2021","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/s0002-9440(10)63132-x","article-title":"Differential Distribution of the JC Virus Receptor-type Sialic Acid in normal Human Tissues","volume":"164","author":"Eash","year":"2004","journal-title":"Am. J. Pathol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1126\/science.1103492","article-title":"The Human Polyomavirus, JCV, Uses Serotonin Receptors to Infect Cells","volume":"306","author":"Elphick","year":"2004","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/978-3-030-20301-6_4","article-title":"Breast Cancer: Current Perspectives on the Disease Status","volume":"1152","author":"Fahad Ullah","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s10719-006-5434-z","article-title":"The Role of Sialic Acid in Human Polyomavirus Infections","volume":"23","author":"Gee","year":"2006","journal-title":"Glycoconj J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/j.celrep.2017.10.027","article-title":"Infectious Entry and Neutralization of Pathogenic JC Polyomaviruses","volume":"21","author":"Geoghegan","year":"2017","journal-title":"Cel Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8036","DOI":"10.18632\/oncotarget.3507","article-title":"The Oncogenic Role of JC Virus T Antigen in Lens Tumors without Cell Specificity of Alternative Splicing of its Intron","volume":"6","author":"Gou","year":"2015","journal-title":"Oncotarget"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.2353\/ajpath.2010.100177","article-title":"Lack of Fetuin-A (\u03b12-HS-Glycoprotein) Reduces Mammary Tumor Incidence and Prolongs Tumor Latency via the Transforming Growth Factor-\u03b2 Signaling Pathway in a Mouse Model of Breast Cancer","volume":"177","author":"Guillory","year":"2010","journal-title":"Am. J. Pathol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1007\/s10549-011-1876-5","article-title":"Investigation of Human JC and BK Polyomaviruses in Breast Carcinomas","volume":"133","author":"Hachana","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"B22","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.virol.2020.06.002","article-title":"Adipocyte Plasma Membrane Protein (APMAP) Promotes JC Virus (JCPyV) Infection in Human Glial Cells","volume":"548","author":"Haley","year":"2020","journal-title":"Virology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1046\/j.1440-1789.2001.00384.x","article-title":"JC Virus Large T Protein Transforms Rodent Cells but Is Not Involved in Human Medulloblastoma","volume":"21","author":"Hayashi","year":"2001","journal-title":"Neuropathology"},{"key":"B24","first-page":"311","article-title":"Survey of Human Polyomavirus (JCV, BKV) Infections in 139 Patients with Lung Cancer, Breast Cancer, Melanoma, or Lymphoma","volume":"105","author":"Hogan","year":"1983","journal-title":"Prog. Clin. Biol. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1007\/0-387-32957-9_20","article-title":"The Polyomavirus, JCV and its Involvement in Human Disease","volume":"577","author":"Khalili","year":"2006","journal-title":"Adv. Exp. Med. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/modpathol.2009.184","article-title":"The Presence of JC Virus in Gastric Carcinomas Correlates with Patient's Age, Intestinal Histological Type and Aberrant Methylation of Tumor Suppressor Genes","volume":"23","author":"Ksiaa","year":"2010","journal-title":"Mod. Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s00428-007-0534-0","article-title":"High JC Virus Load in Tongue Carcinomas May Be a Risk Factor for Tongue Tumorigenesis","volume":"452","author":"Kutsuna","year":"2008","journal-title":"Virchows Arch."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1126\/science.211583","article-title":"Brain Tumors in Owl Monkeys Inoculated with a Human Polyomavirus (JC Virus)","volume":"201","author":"London","year":"1978","journal-title":"Science"},{"key":"B29","doi-asserted-by":"publisher","first-page":"4907","DOI":"10.22034\/APJCP.2016.17.11.4907","article-title":"Evaluation of JC and Cytomegalo Viruses in Glioblastoma Tissue","volume":"17","author":"Malekpour Afshar","year":"2016","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/bjc.2016.285","article-title":"Serum Biomarkers of Polyomavirus Infection and Risk of Lung Cancer in Never Smokers","volume":"115","author":"Malhotra","year":"2016","journal-title":"Br. J. Cancer"},{"key":"B31","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1128\/jvi.49.3.848-856.1984","article-title":"Brain Tumors of Owl Monkeys Inoculated with JC Virus Contain the JC Virus Genome","volume":"49","author":"Miller","year":"1984","journal-title":"J. Virol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1349-7006.2006.00354.x","article-title":"High JC Virus Load in Gastric Cancer and Adjacent Non-cancerous Mucosa","volume":"98","author":"Murai","year":"2007","journal-title":"Cancer Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e35054","DOI":"10.1371\/journal.pone.0035054","article-title":"JC Virus T-Antigen Regulates Glucose Metabolic Pathways in Brain Tumor Cells","volume":"7","author":"Noch","year":"2012","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.3892\/or.2013.2782","article-title":"Pulmonary Tumors Associated with the JC Virus T-Antigen in a Transgenic Mouse Model","volume":"30","author":"Noguchi","year":"2013","journal-title":"Oncol. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1593\/neo.81188","article-title":"JC Virus T-Antigen in Colorectal Cancer Is Associated with P53 Expression and Chromosomal Instability, Independent of CpG Island Methylator Phenotype","volume":"11","author":"Nosho","year":"2009","journal-title":"Neoplasia"},{"key":"B36","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/1348-0421.12372","article-title":"Suppressive Effect of Topoisomerase Inhibitors on JC Polyomavirus Propagation in Human Neuroblastoma Cells","volume":"60","author":"Nukuzuma","year":"2016","journal-title":"Microbiol. Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1007\/s00401-006-0050-3","article-title":"Glioblastoma Multiforme with Small Cell Neuronal-like Component: Association with Human Neurotropic JC Virus","volume":"111","author":"Pi\u00f1a-Oviedo","year":"2006","journal-title":"Acta Neuropathol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1111\/ajt.15663","article-title":"High\u2010grade Urothelial Carcinoma in a Kidney Transplant Recipient after JC Virus Nephropathy: The First Evidence of JC Virus as a Potential Oncovirus in Bladder Cancer","volume":"20","author":"Querido","year":"2020","journal-title":"Am. J. Transpl."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1002\/cncr.25793","article-title":"John Cunningham Virus T-Antigen Expression in Anal Carcinoma","volume":"117","author":"Ramamoorthy","year":"2011","journal-title":"Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1007\/s13365-019-00760-z","article-title":"Diffuse Large B Cell Lymphoma Secondary to JC Virus in Progressive Multifocal Leukoencephalopathy","volume":"25","author":"Reddi","year":"2019","journal-title":"J. Neurovirol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"6517","DOI":"10.1038\/sj.onc.1206959","article-title":"Viruses and Cancer: Lessons from the Human Polyomavirus, JCV","volume":"22","author":"Reiss","year":"2003","journal-title":"Oncogene"},{"key":"B42","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.virol.2010.10.038","article-title":"Interaction and Co-localization of JC Virus Large T Antigen and the F-Box Protein \u03b2-transducin-repeat Containing Protein","volume":"410","author":"Reviriego-Mendoza","year":"2011","journal-title":"Virology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e45000","DOI":"10.1371\/journal.pone.0045000","article-title":"Bag3- Induced Autophagy Is Associated with Degradation of JCV Oncoprotein, T-Ag","volume":"7","author":"Sariyer","year":"2012","journal-title":"PLoS One"},{"key":"B44","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.virol.2020.11.004","article-title":"Human Neurotropic Polyomavirus, JC Virus, Agnoprotein Targets Mitochondrion and Modulates its Functions","volume":"553","author":"Saxena","year":"2021","journal-title":"Virology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1002\/jmv.22240","article-title":"The High Incidence of JC Virus Infection in Urothelial Carcinoma Tissue in Taiwan","volume":"83","author":"Shen","year":"2011","journal-title":"J. Med. Virol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.31557\/apjcp.2020.21.6.1499","article-title":"Prevalence of JC and BK Viruses in Patients with Colorectal Cancer: A Systematic Review and Meta- Analysis","volume":"21","author":"Shoraka","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"15745","DOI":"10.3748\/wjg.v20.i42.15745","article-title":"Could JC Virus Provoke Metastasis in colon Cancer?","volume":"20","author":"Sinagra","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"B48","first-page":"1965","article-title":"Breast Cancer Formation in Transgenic Animals Induced by the Whey Acidic Protein SV40 T Antigen (WAP-SV-T) Hybrid Gene","volume":"8","author":"Tzeng","year":"1993","journal-title":"Oncogene"},{"key":"B49","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1177\/1947601911424578","article-title":"Extinction of Tumor Antigen Expression by SF2\/ASF in JCV-Transformed Cells","volume":"2","author":"Uleri","year":"2011","journal-title":"Genes & Cancer"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13148-010-0013-3","article-title":"Association between hMLH1 Hypermethylation and JC Virus (JCV) Infection in Human Colorectal Cancer (CRC)","volume":"2","author":"Vilkin","year":"2011","journal-title":"Clin. Epigenet"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.3892\/ol.2012.627","article-title":"JC Virus Existence in Chinese Gastrointestinal Carcinomas","volume":"3","author":"Wang","year":"2012","journal-title":"Oncol. Lett."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1016\/j.ejca.2005.08.019","article-title":"Expression of JC Virus Regulatory Proteins in Human Cancer: Potential Mechanisms for Tumourigenesis","volume":"41","author":"White","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"B53","doi-asserted-by":"publisher","first-page":"18303","DOI":"10.18632\/oncotarget.15435","article-title":"Cytokeratin 19 Promoter Directs the Expression of Cre Recombinase in Various Epithelia of Transgenic Mice","volume":"8","author":"Zhao","year":"2017","journal-title":"Oncotarget"},{"key":"B54","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1136\/jcp.2006.040915","article-title":"JC [corrected] Virus Detection in Human Tissue Specimens","volume":"60","author":"Zheng","year":"2007","journal-title":"J. Clin. Pathol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/path.2188","article-title":"Oncogenic Role of JC Virus in Lung Cancer","volume":"212","author":"Zheng","year":"2007","journal-title":"J. Pathol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1471-2334-9-28","article-title":"Mapping the History and Current Situation of Research on John Cunningham Virus - a Bibliometric Analysis","volume":"9","author":"Zheng","year":"2009","journal-title":"BMC Infect. Dis."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.687444\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T09:56:41Z","timestamp":1628762201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.687444\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":56,"alternative-id":["10.3389\/fmolb.2021.687444"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2021.687444","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]},"article-number":"687444"}}