Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma

Abstract

BACKGROUND The human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85–90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T‐antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues. METHODS The authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification. RESULTS JC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and β‐catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser‐capture microdissection verified the presence and specificity of JCV DNA sequences. β‐Catenin and p53 were colocalized with JCV T‐antigen in the nuclei of neoplastic cells. CONCLUSIONS The results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas. Cancer 2005. © 2005 American Cancer Society.

Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model

“…In addition, the JCV DNA has been found in many human tissues including the gastrointestinal track, 10 lung, 11 colon, [5][6][7][8] and esophagus. 9 This indicates that many human tissues maybe susceptible to JCV VLP infection. In this study, human colon cancer cells were subcutaneously injected into nude mice to produce tumors, then JCV VLPs were injected into the mice through the tail vein.…”

“…2,3 In addition, the virus has also been found to be associated with some CNS tumors, such as oligoastrocytoma, oligodendroglioma, and medullablastomas. 4 The virus has also been detected in the upper and lower gastrointestinal tract and other non-neural tumors, such as colon cancers, [5][6][7][8] esophageal cancers, 9 gastric cancers, 10 and lung cancer.…”

The human JC polyomavirus (JCPyV): virological background and clinical implications

“…A number of human malignancies have been associated with JCPyV including oligodendroglioma, astrocytoma medulloblastoma, ependymoma, and glioblastoma (189,(248)(249)(250)(251) and non-Hodgkin lymphoma (252,253), as well as colorectal carcinoma, and gastric and anal cancer (254)(255)(256)(257)(258)(259)(260).…”

IRS‐1–Rad51 nuclear interaction sensitizes JCV T‐antigen positive medulloblastoma cells to genotoxic treatment

“…Since JCV T-antigen has been detected in some medulloblastoma biopsies, 13,40 and its presence sensitizes medulloblastoma cell lines to genotoxic treatments ( Fig. 1), we asked whether JCV T-antigen affects molecular mechanisms responsible for DNA repair of DSBs.…”