Expression of Human Neurotropic Polyomavirus JCV Late Gene Product Agnoprotein in Human Medulloblastoma

Valle, Luis Del; Gordon, Jennifer; Enam, Sahnila; Delbue, Serena; Croul, Sidney; Abraham, Selvajothi; Radhakrishnan, S.; Assimakopoulou, Martha; Katsetos, Christos D.; Khalili, Kamel

doi:10.1093/jnci/94.4.267

Cited by 116 publications

(114 citation statements)

References 28 publications

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“…19,[43][44][45] In several studies, the human neurotropic polyomavirus JC (JCV) DNA has been detected in human brain tumors including medulloblastoma. 13,40,46,47 The oncogenic potential of this virus has been established in experimental animals. Intra-cerebral inoculation of JCV into owl and squirrel monkeys results in astrocytomas.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Dna Repair Of Double Strand Breaksmentioning

confidence: 99%

“…[8][9][10][11] Of interest, PCR-based and immunohistochemical detection of the JC virus (JCV) genome and viral proteins, including JCV T-antigen, has raised questions about the contribution of this common polyomavirus to the development of medulloblastoma. [12][13][14][15] The genomic alterations and possible viral contribution suggest that mechanisms responsible for the maintenance of genomic integrity could be compromised in medulloblastomas. One feasible connection to the development of genomic instability is JCV Tantigen.…”

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confidence: 99%

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

Trojanek

Croul

et al. 2006

Intl Journal of Cancer

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The large T-antigen from human polyomavirus JC (JCV T-antigen) is suspected to play a role in malignant transformation. Previously, we reported that JCV T-antigen requires the presence of a functional insulin-like growth factor I receptor (IGF-IR) for transformation of fibroblasts and for survival of medulloblastoma cell lines; that IGF-IR is phosphorylated in medulloblastoma biopsies and that JCV T-antigen inhibits homologous recombinationdirected DNA repair, causing accumulation of mutations. Here we are evaluating whether JCV T-antigen positive and negative mouse medulloblastoma cell lines, which significantly differ in their tumorigenic properties, are also different in their abilities to repair double strand breaks of DNA (DSBs). Our results show that despite much stronger tumorigenic potential, JCV T-antigen positive medulloblastoma cells are more sensitive to genotoxic agents (cisplatin and c-irradiation). Subsequent analysis of DNA repair of DSBs indicated that homologous recombination-directed DNA repair (HRR) was selectively attenuated in JCV T-antigen positive medulloblastoma cells. JCV T-antigen did not affect HRR directly. In the presence of JCV T-antigen, insulin receptor substrate 1 (IRS-1) translocated to the nucleus where it co-localized with Rad51, possibly attenuating HRR. ' 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Dna Repair Of Double Strand Breaksmentioning

confidence: 99%

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confidence: 99%

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

Trojanek

Croul

et al. 2006

Intl Journal of Cancer

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“…In two separate studies of 43 well-characterized medulloblastomas, nearly 77% were shown to contain viral DNA corresponding to the N-terminal region of JCV T-antigen, while 36% of the tumors analysed by immunohistochemistry showed regions of the tumor with nuclear positivity for T-antigen (Figure 3, Panels a, b, c). In one study, the expression of the JCV late protein, Agnoprotein, was detected in 69% of tumor samples (Del Valle et al, 2002a). Agno is an auxiliary protein whose function remains unclear; however, recently it has been shown to be expressed early in viral infection and can interact with T-antigen to regulate viral transcription and replication (Safak et al, 2001).…”

Section: Association Of Jcv With Human Brain Tumorsmentioning

confidence: 99%

Human neurotropic polyomavirus, JCV, and its role in carcinogenesis

et al. 2003

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A number of recent studies have reported the detection of the ubiquitous human polyomavirus, JC virus (JCV), in samples derived from several types of neural as well as non-neural human tumors. The human neurotropic JCV was first identified as the etiologic agent of the fatal demyelinating disease, progressive multifocal leukoencephalopathy, which usually occurs in individuals with defects in cell-mediated immunity, including AIDS. However, upon mounting evidence of the oncogenic potential of the viral regulatory protein, T-antigen, and JCV's oncogenecity in a broad range of animal models, studies were initiated to determine its potential involvement in human carcinogenesis. Initially, the most frequently observed tumors in rodent models, including medulloblastoma, astrocytoma, glioblastoma, and other neural-origin tumors were analysed. These studies were followed by analysis of non-neural tumors such as colorectal carcinomas. In a subset of each tumor type examined, JC viral genomic DNA sequences could be detected by PCR and confirmed by Southern blot hybridization or direct sequencing. In a smaller subset of the tumors, the expression of T-antigen was observed by immunohistochemical analysis. Owing to the established functions of T-antigen including its ability to interact with tumor suppressor proteins such as Rb and p53, and its ability to influence chromosomal stability, potential mechanisms of JCV T-antigen-mediated cellular dysregulation are discussed. Further, as increasing evidence suggests that T-antigen is not required for maintenance of a transformed phenotype, a hit-and-run model for T-antigen-induced transformation is proposed.

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“…Genomic sequences of these viruses have been reported in different human tumor types. JCV has been found in a large percentage of brain tumors, such as astrocytomas, oligoastrocytomas, glioblastomas, and ependymomas (Kunitake et al, 1995;Rencic et al, 1996;Bofill-Mas and Girones, 2001;Del Valle et al, 2002), in colorectal cancers (Bofill-Mas and Girones, 2001; Del Valle et al, 2002) and in gastric cancers (Shin et al, 2006;Murai et al, 2007). Hachana et al have found that JCV DNA in 23% of BC cases In Tunisian population, and have highlighted the inverse correlation between JCV infection and the expression of estrogen (P = 0.022) and progesterone (P = 0.008) receptors.…”

Section: Tnbc and Virusesmentioning

confidence: 99%

Recent Progress in Triple Negative Breast Cancer Research

Mouh¹,

Mzibri²,

Slaoui³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Triple-negative breast cancer (TNBC) is defined as a type of breast carcinoma that is negative for expression of oestrogene and progesterone hormone receptors (ER, PR) and HER2. This form of breast cancer is marked by its aggressiveness, low survival rate and lack of specific therapies. Recently, important molecular characteristics of TNBC have been highlighted and led to the identification of some biomarkers that could be used in diagnosis, as therapeutic targets or to assess the prognosis. In this review, we summarize recent progress in TNBC research focusing on the genetic and epigenetic alterations of TNBC and the potential use of these biomarkers in the targeted therapy for better management of TNBC.

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Expression of Human Neurotropic Polyomavirus JCV Late Gene Product Agnoprotein in Human Medulloblastoma

Cited by 116 publications

References 28 publications

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

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

Human neurotropic polyomavirus, JCV, and its role in carcinogenesis

Recent Progress in Triple Negative Breast Cancer Research

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