The Oncogenic Roles of JC Virus T Antigen in Breast Carcinogenesis

Abstract

Purpose: JC virus (JCV) infects 80–90% 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.Methods: Breast cancer, dysplasia, and normal tissues were examined for T antigen 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 in situ PCR. T antigen was examined by Western blot using frozen samples of breast cancer and paired normal tissues.Results: According to nested PCR, the positive rate of breast ductal or lobular carcinoma was lower than that of normal tissue (p < 0.05). T antigen existence was negatively correlated with E-cadherin expression and triple-negative breast cancer (p < 0.05), but positively correlated with lymph node metastasis and estrogen receptor and progestogen receptor expression (p < 0.05). Quantitative PCR showed that JCV copies were gradually decreased from normal, dysplasia to cancer tissues (p < 0.05). JCV T antigen copy number was lower in ductal adenocarcinoma than in normal tissue (p < 0.05), in line with in situ PCR and immunohistochemistry. JCV copies were negatively correlated with tumor size and E-cadherin expression (p < 0.05), but positively correlated with G grading of breast cancer (p < 0.05). Western blot also indicated weaker T antigen expression in breast cancer than normal tissues (p < 0.05).Conclusion: 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.

The oncogenic roles of JC polyomavirus in cancer

“…Additionally, we for the first time found that JCPyV was less detectable in cervical epithelium than dysplasia and carcinoma (137). We also observed T antigen DNA and protein in hepatocellular, pancreatic, breast and cervical cancer cells using in situ PCR and immunohistochemistry (134)(135)(136).…”

“…In addition, we reported that the positivity rate and expression levels of T antigen were lower in breast cancer than in normal breast tissue (135), in line with hepatocellular and pancreatic cancer (136). T antigen DNA positivity was inversely associated with E-cadherin expression and triple-negative breast cancer but positively associated with lymph node involvement and ER and PR expression.…”

Virus-host interaction analysis in colorectal cancer identifies core virus network signature and small molecules

“…VE6 in HPV16 and HPV18 promotes cell cycle deregulation leading to malignancy [63] . The large T antigen supports viral replication and carcinogenesis [64] , [65] . Functional enrichment analysis of this refined network showed that it is enriched in the cell cycle, apoptosis, and signaling pathways ( Supplementary Table S1 ).…”

Traces of JC polyomavirus in papillary thyroid cancer: a comprehensive study in Iran

“…The viral etiology of human cancers is an interesting topic, and to date, several virus types have been identified in human cancers. JCPyV infects most of the world's population, with 80%-90% of adults being serum-positive [17]. Cell infection by JCPyV has two possible outcomes, including lytic infection in permissive cells that allows viral DNA replication and oncogenesis in nonpermissive cells, which do not support viral DNA replication resulting in incomplete infection or malignant cell transformation [18].…”

“…Cell infection by JCPyV has two possible outcomes, including lytic infection in permissive cells that allows viral DNA replication and oncogenesis in nonpermissive cells, which do not support viral DNA replication resulting in incomplete infection or malignant cell transformation [18]. Previous studies indicated a feasible role of JCPyV in several cancers, namely brain cancers of medulloblastomas and glial origin, as well as epithelial cancers, such as colon, prostate, breast, and lung adenocarcinoma, and esophageal carcinomas [10,13,17,19,20].…”