Oncogenic T‐antigen of JC virus is present frequently in human gastric cancers

Abstract

BACKGROUND. JC virus (JCV) is a polyomavirus that commonly infects humans and is the causative agent of progressive multifocal leukoencephalopathy in immune‐compromised patients. An association between JCV and human cancers long has been suspected, because this virus induces brain tumors in several animal models. The oncogenic potential of JCV is mediated by a transforming protein, the T‐antigen (T‐Ag), which is a multifunctional protein that transforms cells through interactions with various growth‐regulatory genes, including p53 and pRb, and by stabilizing β‐catenin. Previously, the laboratory at the authors' institution demonstrated that JCV is present frequently in the human gastrointestinal tract and may play a role in colorectal carcinogenesis. However, to date, no studies have determined whether JCV sequences are present specifically in gastric cancers. The current study was designed to investigate whether JCV sequences and expression are found in human gastric cancers. METHODS. DNA was extracted from 23 paraffin embedded and 14 frozen gastric cancer specimens. For the detection of JCV gene sequences, polymerase chain reaction amplifications were performed using gene‐specific primers for T‐Ag, VP‐1 (a JCV capsid gene), and the viral regulatory region (or transcriptional control region). Immunohistochemical staining was performed with an anti‐T‐Ag monoclonal antibody to detect protein expression. RESULTS. Twenty‐one of 37 gastric cancers (57%) harbored JCV T‐Ag sequences, and 13 of 37 gastric cancers (30%) contained VP‐1 sequences. T‐Ag sequences also were found in adjacent nonneoplastic mucosa. In addition, JCV regulatory region sequences were present frequently in gastric cancers and adjacent nonneoplastic mucosa. T‐Ag protein expression was found in 9 of 23 gastric cancers (39%), whereas no expression was observed in any of the nonneoplastic tissues. CONCLUSIONS. To the authors' knowledge, this is the first demonstration of the presence of JCV T‐Ag expression in human gastric cancers. These findings suggest a possible role for this polyomavirus in gastric carcinogenesis. Cancer 2006. © 2006 American Cancer Society.

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

“…Another plausible explanation for this inconsistency is that JCV-associated gastric carcinomas may show a variation in geographic distribution because of ethnic diversity, genetic predisposition and/or environmental factors. The low frequency of JCV T-antigen sequences detected in non-neoplastic gastric mucosa from Tunisian patients in comparison with those reported earlier 15,16 argues for a geographic variation in virus distribution. Overall, our results are in agreement with previous findings that report the presence of JCV DNA sequences in the mucosa of the gastrointestinal tract and in gastric cancers.…”

“…However, the detection rate of JCV as a total (26%) was lower than that reported in recent studies in gastric carcinomas (57-86%). 15,16 One possible explanation for these discrepant results is likely caused by difference in the DNA quality, as suggested by Murai et al 16 the detection rate of JCV sequences is severely reduced in formalin-fixed and paraffin-embedded tissues compared with fresh tissues. Another plausible explanation for this inconsistency is that JCV-associated gastric carcinomas may show a variation in geographic distribution because of ethnic diversity, genetic predisposition and/or environmental factors.…”

“…12 Several recent studies have suggested a potential role of JCV in colorectal carcinomas 13,14 and gastric cancers. 15,16 Reports regarding the other polyomaviruses have shown that BKV induces nephropathy, disease usually developed under conditions of severe cellular immunosuppression, while the presence of SV40 was associated with several types of human neoplasms including pleural mesotheliomas, osteosarcomas and lymphomas. [17][18][19] The oncogenic potential of polyomaviruses is mediated by the viral regulatory T-antigen that can dysregulate control of the cell cycle by sequestering and inactivating the cellular tumor suppressor proteins p53 and members of the pRb family.…”

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.…”

“…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.…”