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.