Disease relevance of tAg

• BACKGROUND: Evidence that simian virus 40 (SV40) is associated with human mesotheliomas, osteosarcomas, and brain tumors suggests that a recombinant vaccine directed against lethal cancers expressing SV40 T antigen (Tag) could have clinical utility [1].
• Transgenic animals harboring the early SV40 coding region (T/t-antigen) under the transcriptional control of the WAP promoter develop breast cancer after the first lactation period [2].
• Transgenic mice expressing SV40 large T-antigen (Tag) oncogene in beta-cells develop tumours in a multi-stage progression from hyperplasia, angiogenesis, to solid encapsulated tumours [3].
• Growth occurred more slowly and to lower titers than is seen with the prototypical PML JCV strain Mad-1, with relatively few cells containing viral T antigen (T-Ag) or viral capsid protein, Vp1 [4].
• Cells transformed by Polyoma virus (Py) can undergo a high rate of excision or amplification of integrated viral DNA sequences, and these phenomena require the presence of homology (i.e., repeats) within the viral insertion as well as a functional viral large T antigen (T-Ag) [5].

High impact information on tAg

• To determine whether the main role of large T-Ag in excision and amplification was replicative or recombination-promoting, we studied transformed rat cell lines containing tandem insertions of a ts-a Py molecule (encoding a thermolabile large T-Ag) with a deletion of the origin of viral DNA replication [5].
• All G418-resistant clones analyzed readily amplified the integrated plasmid molecules when grown under conditions permissive for large T-Ag function, showing that these cells produced viral large T-Ag capable of promoting amplification in trans of DNA sequences containing the Py origin [5].
• JCV encodes a "transforming" gene, T-antigen (T-Ag), which is believed to mediate the oncogenic potential of the virus [6].
• Significant associations were observed between T-Ag expression and CIN in CRCs (P = .017) and between T-Ag expression and promoter methylation of multiple genes (P = .01) [6].
• CONCLUSIONS: The association between T-Ag expression and promoter methylation in CRC suggests that this viral oncogene may induce methylator phenotype and that JCV may be involved in CRC through multiple mechanisms of genetic and epigenetic instability [6].

Chemical compound and disease context of tAg

• Treatment of mouse embryo (ME) cells with 5-iodo-2'-deoxyuridine (IdUrd) before infection with SV40 virus, enhances T-antigen (T-Ag) production as detected by immunofluorescence and complement fixation [7].
• In HeLa cells stably transfected with the reporter gene and interacting (p53-TAg) or noninteracting (p53 and polyoma virus coat protein) pairs of proteins, treatment with doxycycline produced time- and dose-dependent increases in expression of hybrid proteins [8].
• Androgen-dependent prostate epithelial cell selection by targeting ARR(2)PBneo to the LPB-Tag model of prostate cancer [9].
• Formalin-fixed, paraffin-embedded cell block sections from 100 pleural effusions (32 MMs, 25 benign reactive, 43 metastatic adenocarcinomas) were immunostained for the SV-40 anti-Tag, using two primary monoclonal SV-40 Tag antibodies: clone Pab 416 and clone Pab 101 [10].

Biological context of tAg

• RESULTS: JCV T-Ag DNA sequences were found in 77% of the CRCs and 56% of these cancers (or 43% of the total) expressed T-Ag by IHC [6].
• The ability of T antigen to functionally cooperate with Tst-1 was contained within its N-terminal region, shown by the fact that small tumor antigen (t antigen) could substitute for T antigen in transfection experiments [11].
• We also report that the dominant inhibitory effect is caused by the DNA-dependent protein kinase (DNA-PK) which inactivates SV40 T antigen (TAg) by phosphorylation [12].
• Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin [13].
• BKV sequences and T antigen (Tag) are detected in several types of human neoplasms, although the viral load is generally low, with less than one copy of the viral genome per cell [14].

Anatomical context of tAg

• In a recently developed cell line, denoted betaTC-tet, derived from transgenic mice expressing the SV40 T antigen (Tag) under control of the tetracycline (Tc) gene regulatory system, growth arrest can be induced by shutting off Tag expression in the presence of Tc [15].
• To asses the requirement of interleukin (IL)-10 for peripheral CD4 T cell tolerance, the IL-10 knockout (KO) was introduced into a T cell receptor-transgenic mouse model (TCR1) specific for SV40 T antigen (Tag) [16].
• When differentiation was triggered, Tag expression reduced the formation of myotubes and dead cells showing apoptotic features were present [17].
• The effect of bcl-2 expression on genetically programmed photoreceptor degeneration was evaluated by crossing these transgenic mice with mice that develop a rapid degeneration of rod photoreceptors due to expression of a distinct transgene, SV40 T antigen (Tag) [18].
• The simian virus 40 small tumor antigen (t antigen) gene has been cloned downstream from a hybrid Escherichia coli trp-lac promoter and a suitable ribosome binding site [19].

Associations of tAg with chemical compounds

• Upon acute infection, the frequency of mutation to 8AZ resistance was raised at most by two- to eightfold over the spontaneous frequency, and it was independent of the presence of a functional 90,000-molecular-weight T antigen or 20,000-molecular-weight t antigen or both [20].
• When either this fraction (freed of urea) or NaDodSO4 gel-purified 865i t antigen (rendered free of detergent) was injected into untransformed rat cells, dissolution of intracellular actin cable networks was observed [19].
• 2-difluoromethylornithine and dehydroepiandrosterone inhibit mammary tumor progression but not mammary or prostate tumor initiation in C3(1)/SV40 T/t-antigen transgenic mice [21].
• Mutations were generated in Py T Ag whereby either or both threonines were replaced with alanine, generating T187A, T278A, and double-mutants (DM [T187A T278A]) mutant T Ags [22].
• Prostatic lesions developed in these mice in a predictable and heritable manner, indicating that Neo did not alter Tag-induced prostate tumor development and progression [9].

Analytical, diagnostic and therapeutic context of tAg

• PCR amplifications were performed for T-Ag sequences, and immunohistochemical (IHC) staining was performed to detect T-Ag expression [6].
• When monoclonal antibodies or antisera against T antigen (T Ag) were added to SV40 chromosomes or when T Ag, both free and chromatin bound, was removed by immunoprecipitation with anti-T, the activity of the late promoter remained essentially unchanged [23].
• TSTA is defined by SV40-specific transplantation immunity, whereas T-antigen (T-Ag) can be detected serologically by indirect immunofluorescence [24].
• After gel filtration of such t antigen-enriched solutions, highly purified protein was obtained [19].
• SV40 Tag expression was revealed by immunohistochemistry with the specific monoclonal antibody Pab 101 in PA thin sections with a highly sensitive technical approach which retrieved the nuclear viral oncoprotein in 26 out of 28 (93%) samples previously found SV40-positive by PCR [25].

References