Disease relevance of Tag

• The transgenic adenocarcinoma of mouse prostate (TRAMP) model is transgenic for the SV40 large T Ag (Tag) under the control of the rat probasin regulatory elements [1].
• In these mice, Tag expression elicits both beta cell hyperplasia with subsequent progression to tumors and lymphocytic infiltration [2].
• Simian virus 40 T (tumor) antigen (Tag) with its own natural enhancer causes choroid plexus tumors in mice [3].
• To test whether this lack of LN metastases reflects their absence from the circulation, transgenic mice were produced that express Tag (T), L-selectin (L), and Escherichia coli LacZ (Z), in pancreatic beta cells [4].
• RIP1-Tag2 mice, which express Tag as embryos, are tolerant to Tag, whereas RIP1-Tag4 mice, which express the transgene in pancreatic islet beta cells several weeks after birth and develop insulinomas, can be immunized to generate active Tag-specific cytotoxic T lymphocytes as determined by in vitro assays [5].

High impact information on Tag

• The CaBP9K regulatory sequences directing the expression of the Tag gene possess an estradiol responsive element, and accordingly, development of the tumors was strictly under the control of estrogen [6].
• The distinct cerebellar phenotypes of the SV4-6 lines correlate with specific Tag-induced Purkinje cell ablation as opposed to tumorigenesis [7].
• However, after the transgene is expressed, RIP1-Tag4 mice are unable to mount a tumor-inhibiting response upon immunization, although Tag-specific cytotoxic T cells can still be demonstrated in vitro [5].
• Indeed, RIP1-Tag4 mice immunized with Tag by SV40 infection prior to the time of endogenous transgene expression also mount an effective in vivo cellular immune response to the Tag-expressing pancreatic beta cells, and Tag-induced tumor growth is significantly delayed (up to 1 year) [5].
• Transgenic mice expressing T antigen (Tag) in pancreatic beta cells establish systemic tolerance toward this self-protein [8].

Chemical compound and disease context of Tag

• Forty-eight transgenic BLH-SV40 Tag retinoblastoma mice were administered five intravitreal injections of carboplatin in one eye [9].
• Although testosterone treatment was able to induce interstitial cell hyperplasia in gonads of the Inh-alpha/Tag mice, direct gonadotropin action is responsible for gonadal and adrenal tumorigenesis [10].
• The single (Inhalpha/Tag) and double TG (Inhalpha/TK-Inhalpha/Tag) mice, both bearing gonadal tumors, were treated at the age of 5.5-6.5 months with ganciclovir (GCV, 150 mg/kg body weight twice daily i.p.) for 14 days, or with aciclovir (ACV, 300-400 mg/kg body weight per day perorally) for 2 months [11].

Biological context of Tag

• These mice have impaired antibody responses to Tag, show diminished Tag-specific T-cell proliferation, and evidence an inability to generate Tag-specific cytotoxic T cells [8].
• The self-tolerance in two families of rat insulin promoter (RIP)-Tag mice, expressing different levels of Tag protein, has been characterized [8].
• Twenty-one of 32 (66%) mice aged > or = 6 months and 15 of 17 (88%) mice aged > or = 9 months developed metastatic tumors, as confirmed by histology and/or Tag immunohistochemistry [12].
• Thus, the expression of Tag in intestinal goblet cells releases them from normal antiproliferative controls, causing their inappropriate entry into S phase even after they transverse the crypt/villus junction [13].
• KIM-2 cells were generated using a temperature sensitive T-antigen (Tag) and studies at the permissive temperature (33 degrees C) have shown that a Tag binding protein was essential for this apoptotic response [14].

Anatomical context of Tag

• To test this hypothesis we introduced an enhancerless Tag gene downstream of a LCR cassette into the germ lines of mice [3].
• A line of mice was established (MUCTag6) that expressed Tag in intestinal goblet cells as determined by RNA blot and immunohistochemical analysis [13].
• Whereas Tag is expressed uniformly in prostate epithelium, only an increasing subset of cells in prostatic intraepithelial neoplasia showed NE differentiation by chromogranin immunostaining [12].
• Tyrp1-Tag mice that develop early vascularized tumors of the retinal pigment epithelium were crossed with tyrp1-FGFR1-DN mice that express dominant-negative FGF receptors in the retinal pigment epithelium to generate bigenic mice [15].
• By contrast, at a later stage when tyrp1-Tag tumors rapidly expanded to fill the entire eye posterior chamber and migrate along the optic nerve toward the chiasma, bigenic tumors remained small and were poorly vascularized [15].

Associations of Tag with chemical compounds

• As the expression of Tag transcripts is controlled by D-glucose, the structural and physiological characteristics of these cell lines can be studied in either quiescent or active growth conditions [16].
• To study further the role of luteinizing hormone (LH) in gonadal and adrenal tumorigenesis, a double TG mouse model was generated by crossing the Inhalpha/Tag mice with mice producing constitutively elevated levels of LH (bLHbeta-CTP mice) [17].
• To achieve efficient and regulated mutagenesis, we constructed Enhanced Retroviral Mutagen (ERM) vectors that contained several engineered sequences (e.g., an ERM Tag and a splice donor) controlled by a tetracycline-responsive promoter [18].
• Replacement of D-glucose by neoglucogenic substrates (lactate, oxaloacetate) blunted the expression of Tag transcripts and induced arrest of cell growth [16].
• Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice [19].

Physical interactions of Tag

• Tag-p53 and Tag-pRb complexes were screened in 18 and 15 Tag positive tumor tissues, respectively [20].

Regulatory relationships of Tag

• In contrast, TGF-beta inhibited Tag expression [21].

Other interactions of Tag

• The d11137 Tag mutant protein, which inhibits pRb function without affecting p53, induced hepatic tumours [22].
• In contrast, only one of the eight Tag/Ghr(-/-) mice exhibited atypia (P < 0.01, Fischer's exact test) [23].
• In contrast, only a few differentiated cells were observed in the presence of TGF beta 1 and Tag [24].
• Transgenic (TG) mice expressing the Simian virus 40 T-antigen under the control of the murine inhibin-alpha promoter (Inhalpha/Tag) develop granulosa and Leydig cell tumors at the age of 5-6 months, with 100% penetrance [17].
• We conclude that in the Inhalpha/Tag tumor mouse model, elevated LH levels act as a tumor promoter, advancing gonadal and adrenal tumorigenesis [17].

Analytical, diagnostic and therapeutic context of Tag

• In addition, the adoptive transfer of spleen cells from Tag-immune C57BL/6 mice resulted in a dramatic increase in the control of tumor progression in SV11 mice and was associated with the accumulation of CD8(+) T cells specific for multiple Tag epitopes in the brain [25].
• In a classical vaccination protocol, Tag was administered with CpG-ODN as adjuvant [26].
• The DNA synthesis, as well as the levels of inhibin-alpha and Tag mRNA expression, were significantly reduced by recombinant human inhibin A in cell cultures derived from the adrenal tumors [27].
• Results from Northern blot analysis indicate that the expression of the T antigen gene (Tag) is dependent on the concentration of D-glucose in the medium and show that the L-PK construct has maintained its capacity for up- or down-regulation by carbohydrates [16].
• In this study we investigated SV40 large T antigen (SV40 Tag) protein expression in mesothelioma cell lines, established in our laboratory, by Western blotting, immunoprecipitation, and immunocytochemistry using Tag-specific mouse monoclonal antibodies (mAbs) Ab-1 (or Pab 419) [28].

References