ABCB2 p.Thr98Gly
| Predicted by SNAP2: | A: N (72%), C: N (66%), D: N (57%), E: N (61%), F: D (63%), G: N (57%), H: N (57%), I: N (57%), K: D (53%), L: N (53%), M: N (57%), N: N (72%), P: N (82%), Q: N (61%), R: D (59%), S: N (82%), V: N (82%), W: D (80%), Y: D (59%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, V: N, W: N, Y: N, |
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[hide] HMME-based PDT restores expression and function of... J Neurooncol. 2011 Nov;105(2):199-210. Epub 2011 Apr 26. Zhang SY, Li JL, Xu XK, Zheng MG, Wen CC, Li FC
HMME-based PDT restores expression and function of transporter associated with antigen processing 1 (TAP1) and surface presentation of MHC class I antigen in human glioma.
J Neurooncol. 2011 Nov;105(2):199-210. Epub 2011 Apr 26., [PMID:21520005]
Abstract [show]
Numerous studies have established that photodynamic therapy (PDT) can trigger tumor-specific immunity and cancer cell immunogenicity, both of which play a critical role in the long-term control of oncogenesis; however, the underlying mechanisms are largely unexplained. Deficiency of the transporter associated with antigen processing 1 (TAP1) has been observed in a variety of tumors, and the question has been raised whether the restoration of TAP1 could facilitate the activation of antitumor immunity. To elucidate the mechanisms underlying PDT-induced immunopotentiation, we examined the hypothesis that upregulating TAP1 via PDT may contribute to enhancement of antitumor immunity and cancer cell immunogenicity. In this study, we investigated the effects of PDT on the expression and function of TAP1 in glioma cells. We found that HMME-based PDT restored TAP1 expression in a rapid and transient manner. Furthermore, the newly synthesized TAP1 protein was capable of potentiating the activity of transporting antigen peptides. As a result, restoration of the expression and function of TAP1 translated into augmenting the presentation of surface MHC class I molecules. Overall, our data indicate that PDT enables glioma cells to recover both the expression of functional TAP1 and the presentation of surface MHC class I antigens, which are processes that may enhance antitumor immunity after PDT. These findings may have implications for PDT and provide new insights into the mechanisms underlying PDT-induced immunopotentiation.
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No. Sentence Comment
48 Materials and methods Cells and reagents Three human glioma cell lines (U87, U251, and T98G) were obtained from the Animal House of Sun Yat-sen University (Guangzhou, China).
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ABCB2 p.Thr98Gly 21520005:48:87
status: NEW86 In-vitro peptide transport assay Peptide transport in permeabilized U251, U87, and T98G cells was measured as described previously for EC and HeLa cells, with minor modifications [30].
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ABCB2 p.Thr98Gly 21520005:86:83
status: NEW109 Results Cytotoxic effects of PDT on human glioma cell lines To determine the cytotoxic effects of PDT on the growth of tumor cells, U251, U87, and T98G cells in the exponential growth phase were incubated for 24 h with 10 lg/mL HMME (the maximum non-toxic concentration).
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ABCB2 p.Thr98Gly 21520005:109:147
status: NEW132 U251, U87, and T98G cells in exponential growth phase were incubated for 24 h with 10 lg/mL HMME (the maximum innocuous concentration).
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ABCB2 p.Thr98Gly 21520005:132:15
status: NEW148 As shown in Fig. 4, untreated U251 cells (a), U87 cells (b) and T98G cells (c) all expressed barely detectable levels of TAP1.
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ABCB2 p.Thr98Gly 21520005:148:64
status: NEW173 c TAP1 protein was detected in T98G cell lines.
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ABCB2 p.Thr98Gly 21520005:173:31
status: NEW223 Three tumor cell lines (U251, U87, and T98G) were treated with HMME-PDT (2.4 J/cm2 ?
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ABCB2 p.Thr98Gly 21520005:223:39
status: NEW[hide] WHO grade associated downregulation of MHC class I... Acta Neuropathol. 2007 Aug;114(2):111-9. Epub 2007 May 31. Mehling M, Simon P, Mittelbronn M, Meyermann R, Ferrone S, Weller M, Wiendl H
WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas: does it reflect a potential immune escape mechanism?
Acta Neuropathol. 2007 Aug;114(2):111-9. Epub 2007 May 31., [PMID:17541610]
Abstract [show]
Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with grade of malignancy. Quantitative immunohistochemical analysis of astrocytomas revealed reduced expression of the cytosolic proteasome subunit low molecular weight protein 2 (LMP2), the endoplasmatic reticulum (ER) transporter associated with antigen processing-1 (TAP1), and the ER chaperone beta2-microglobulin (beta2m) in astrocytoma cells when compared to astrocytes from nonpathological brain. Among human WHO grade II-IV astrocytomas, downregulation of LMP2, TAP1 and beta2m correlated with grade of malignancy. Furthermore, astrocytoma cell lines (n = 12) expressed all APM components analyzed at levels comparable to dendritic cells (DC), which were used for comparative purposes. However, upregulation of beta2m after stimulation with inflammatory cytokines was significantly lower in astrocytoma cell lines than in control cells. Our results support the hypothesis that coordinated downregulation or impaired upregulation of certain HLA class I APM components may serve as a mechanism for astrocytoma cells to evade the host's immune response, even if HLA class I antigen surface expression is not altered.
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42 Cell lines The human glioma cell lines A172, D247MG, LN-18, LNT-229, LN-308, LN-319, LN-428, T98G, U87MG, U138MG, U251MG, and U373MG (kindly provided by Dr. N. de Tribolet, Neurosurgical Service, Centre Hospitalier Universitaire, Vaudois, Lausanne, Switzerland) were cultured in 75 cm3 Falcon plastic Xasks (BD Biosciences, Heidelberg, Germany) using DMEM supplemented with 1% glutamine (Life Technologies, Paisley, UK), 10% FCS (Biochrom, Berlin, Germany), and penicillin (100 IU/ml)/ streptomycin (100 g/ml) (Life Technologies) [49].
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ABCB2 p.Thr98Gly 17541610:42:93
status: NEW[hide] Reduced expression of the transporter associated w... J Neurosurg. 2006 Feb;104(2):264-71. Satoh E, Mabuchi T, Satoh H, Asahara T, Nukui H, Naganuma H
Reduced expression of the transporter associated with antigen processing 1 molecule in malignant glioma cells, and its restoration by interferon-gamma and -beta.
J Neurosurg. 2006 Feb;104(2):264-71., [PMID:16509500]
Abstract [show]
OBJECT: It remains unclear whether malignant glioma cells can deliver tumor antigens efficiently to major histocompatibility complex (MHC) Class I molecules. To elucidate the mechanism of antigen presentation in malignant gliomas, the authors examined the expression of the transporter associated with antigen processing 1 (TAP1), which transports antigens to MHC Class I molecules, and low-molecular-mass polypeptide 2 (LMP2), which is a subunit of a proteasome. They also analyzed the effects of interferon (IFN)-gamma and IFN-beta on the expression of these molecules. METHODS: Five glioma cells expressed undetectable or very low levels of TAP1 protein and did not express TAP1 messenger (m)RNA. Normal brain tissue and glioma tissue specimens also showed undetectable levels of TAP1 protein and the same levels of LMP2 protein as lymphoblastoid B cells. Treatments of the tumor cells with IFN-gamma, or -beta enhanced the expression of both TAP1 protein and mRNA as well as the expression of MHC Class I molecules. The expression of LMP2 protein was not altered by the IFN treatments. The authors analyzed structural alterations in the TAP1 promoter region in eight malignant glioma cell lines. Single nucleotide polymorphism was found in 446 bp up-stream of the translation start site of the TAP1 gene, and a point mutation was found in 34 bp upstream of the TAP1 gene. CONCLUSIONS: Malignant glioma cells may be less immunogenic due to low levels of TAP1 expression. Upregulated expression of TAP1 and MHC Class I molecules by IFN-gamma and -beta may enhance antigen presentation in malignant glioma cells.
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22 Materials and Methods Cell Culture, Tissue Samples, and Reagents Three human GBM cell lines (A172, U251, and T98G) and a mixed glioma cell line (KG1C) were obtained from the Japanese Cancer Resources Bank (Tokyo, Japan).
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ABCB2 p.Thr98Gly 16509500:22:109
status: NEW77 Four glioma cell lines (A172, KG1C, YMG2, and YMG4) showed T and T in alleles, two cell lines (T98G and YMG5) G and T (Fig. 4), and two cell lines (U251 and YMG1) G and G.
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ABCB2 p.Thr98Gly 16509500:77:95
status: NEW78 Four glioma cell lines (A172, KG1C, YMG2, and YMG4) showed T and T in alleles, two cell lines (T98G and YMG5) G and T (Fig. 4), and two cell lines (U251 and YMG1) G and G.
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ABCB2 p.Thr98Gly 16509500:78:95
status: NEW[hide] Identification of the osteopontin gene as a direct... Genes Chromosomes Cancer. 2002 Mar;33(3):270-8. Morimoto I, Sasaki Y, Ishida S, Imai K, Tokino T
Identification of the osteopontin gene as a direct target of TP53.
Genes Chromosomes Cancer. 2002 Mar;33(3):270-8., [PMID:11807984]
Abstract [show]
The TP53 tumor suppressor gene regulates a number of genes that are involved in cell-cycle inhibition, apoptosis, and maintaining genetic stability. Recently, two genes that have a role in immunosurveillance were identified as downstream targets of TP53. These genes, TAP1 and fractalkine, may contribute to suppress tumor growth through host immunosurveillance. It has been reported that the mouse secreted phosphoprotein osteopontin (Opn) is one of the key cytokines for type 1 immune responses mediated by macrophages. It also was reported that Opn may play a role in suppressing tumor growth in vivo. Here we identified Opn as a Tp53-target gene using mRNA differential display analysis of embryonic fibroblasts from Tp53-deficient mice. Furthermore, we found that Opn expression was upregulated by DNA damage-induced Tp53 activity and by adenovirus-mediated transfer of the human TP53 gene. In addition, a luciferase assay showed that the Opn gene has a functional Tp53-responsive element in its promoter region, and a chromatin immunoprecipitation assay confirmed interaction between the Opn promoter and Tp53 protein in vivo. These results suggest that OPN is a direct transcriptional target of TP53. The TP53-directed regulation of OPN expression suggests a novel model of TP53 participation in immunosurveillance, involving interaction with the host immune system to prevent damaged cells from undergoing malignant transformation.
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No. Sentence Comment
28 Human tumor cell lines A172 (glioblastoma), T98G (glioblastoma), Saos2 (osteosarcoma), HCT116 (colorectal carcinoma), and H1299 (non-small-cell lung carcinoma) were purchased from the American Type Culture Collection (Rockville, MD).
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ABCB2 p.Thr98Gly 11807984:28:44
status: NEW32 A172, T98G, and Saos2 cells were incubated continuously with adriamycin at 0.2 g/mL.
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ABCB2 p.Thr98Gly 11807984:32:6
status: NEW[hide] Rescue of MHC-1 antigen processing machinery by do... PLoS One. 2013;8(3):e58428. doi: 10.1371/journal.pone.0058428. Epub 2013 Mar 20. Pan Y, Trojan J, Guo Y, Anthony DD
Rescue of MHC-1 antigen processing machinery by down-regulation in expression of IGF-1 in human glioblastoma cells.
PLoS One. 2013;8(3):e58428. doi: 10.1371/journal.pone.0058428. Epub 2013 Mar 20., [PMID:23526983]
Abstract [show]
Escape from immune recognition has been hypothesized to be a factor in carcinogenesis. It may be mediated for many cancers through down-regulation in the MHC class 1 antigen processing and presentation pathway. TAP-1, TAP-2, tightly linked to LMP-2 and LMP-7 are multiple components of the endogenous, antigen presentation pathway machinery. We addressed the question of alterations in this pathway in human Glioblastoma (HGB) and of its relationship to modulation in expression of IGF-1 that is highly expressed in this cancer. Deficiencies in expression of TAP-1 were demonstrated by RT-PCR and/or by immuno-flow cytometry in the HGB cell line T98G obtained from ATCC, and in 3 of 4 human cell lines established from patients with Glioblastoma Multiforme. Deficiencies in expression of TAP-2 were observed in 3 of 4, deficiencies in expression of LMP-2 in 4 of 4 and deficiencies in LMP-7 in 3 of 4 HGB cell lines examined by RT-PCR and Western blot. Following down-regulation of IGF-1 by transfection with the pAnti IGF-1 vector that expresses IGF-1 RNA in antisense orientation, or by the exogenous addition of IGF-1 receptor monoclonal antibody to cell culture media, the deficiencies in components of the MHC-1 antigen presentation pathway were up-regulated and/or rescued in all HGB cell lines tested. Moreover, this up-regulation in expression was aborted by addition of 100 ng/ml of IGF-1 to the culture media. Unlike in the case of IFN-gamma, the restoration of TAP-1 and LMP-2 by down-regulation of IGF-1 in Glioblastoma cells was not correlated to the tyrosine phosphorylation of STAT 1. In summary, the simultaneous reversion in expression of the multiple constituents of MHC-1 antigen processing path and up-regulation in expression of MHC-1 occurring with down-regulation in IGF-1 may have a role in reinforcement of immunity against tumor antigen(s) in some animal cancers and in humans with Glioblastoma Multiforme.
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218 Down-regulation in Expression of TAP-1 in pAnti IGF-1 Transfected HGB Cells by Exogenous Addition of IGF-1 Occurs with Inhibition of Phosphorylated STAT3(Tyr 705) and in Absence of Phosphorylated STAT1(Tyr 701) In order to determine whether Stat signaling is involved in the IGF-1 regulated expression of the TAP-1 gene, the pAnti IGF-1 transfected T98G and/or HG-2 cells were treated with addition of IGF-1 (100 ng/ml) in absence of serum and with ZnSO4 (50uM) added to culture medium.
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ABCB2 p.Thr98Gly 23526983:218:349
status: NEW230 The expression of pStat1 in T98G NT (data not shown) and T98G TX cells was not detected; and it was also not detected after the exogenous addition of IGF-1 (Fig 7 B, C).
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ABCB2 p.Thr98Gly 23526983:230:28
status: NEWX
ABCB2 p.Thr98Gly 23526983:230:57
status: NEW231 In contrast, pStat3 was expressed in both T98G NT (data not shown) and T98G TX cells; and it was transiently decreased following addition of IGF-1 to T98G TX cells for a limited time interval (Fig 7 B, C).
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ABCB2 p.Thr98Gly 23526983:231:42
status: NEWX
ABCB2 p.Thr98Gly 23526983:231:71
status: NEWX
ABCB2 p.Thr98Gly 23526983:231:150
status: NEW243 A, Regulation of TAP-1 peptide in T98G and HG-2 TX cells was determined by Western Blot.
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ABCB2 p.Thr98Gly 23526983:243:34
status: NEW246 Lanes 1, 2 are NT cells from the T98G and HG-2 cell lines respectively. Lane 3, 4 are TX cells from clone b and c of the T98G cell line; Lane 5, 6 are TX cells from clone 5 and 11 of the HG-2 cell line.
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ABCB2 p.Thr98Gly 23526983:246:33
status: NEWX
ABCB2 p.Thr98Gly 23526983:246:121
status: NEW251 Lanes 1, 2 and 3 represent T98G, HG-2 and HG-9 cell lines cultured in medium with no IGF-1R mAb added, while lanes 4, 5 and 6 are the corresponding respective cell lines cultured in medium with addition of exogenous IGF-1R mAb (10ug/ml), respectively.
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ABCB2 p.Thr98Gly 23526983:251:27
status: NEW253 Row 5 demonstrates the rescue in expression of the B-7.1 peptide in IGF-1R mAb treated T98G, HG-2 and HG-9 cell lines when compared to the wild types of the corresponding non-treated cells.
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ABCB2 p.Thr98Gly 23526983:253:87
status: NEW263 In addition, and importantly, similar results were obtained using the ATCC T98G stably cloned cell line of Glioblastoma as a standard control.
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ABCB2 p.Thr98Gly 23526983:263:75
status: NEW275 Different clones of transfected (TX) and corresponding non-transfected (NT) HGB cell lines, eight from T98G (circles), two from HG-2 (rectangles) and one from HG-3 (triangle), were examined by flow cytometry for the expression of TAP-1.
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ABCB2 p.Thr98Gly 23526983:275:103
status: NEW279 T98G cells were transfected with the vector containing antisense IGF-1 cDNA (TX pAnti IGF-1), with vector containing antisense IGF-2 cDNA (TX pAnti IGF-2), or, with vector containing no antisense sequence (TX pEMT).
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ABCB2 p.Thr98Gly 23526983:279:0
status: NEW280 Transfected cells were comparatively examined by flow cytometry relative to non-transfected T98G cells (NT) for content of TAP-1.
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ABCB2 p.Thr98Gly 23526983:280:92
status: NEW290 Firstly, pSTAT 3 was detected in pAnti IGF-1 transfected, IGF-1 down-regulated T98G cells.
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ABCB2 p.Thr98Gly 23526983:290:79
status: NEW292 These data show that STAT 3 may have a tumor-suppressive function in Glioblastoma cells, such as in the T98G cell line.
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ABCB2 p.Thr98Gly 23526983:292:104
status: NEW298 PAkt was not detectable in pAnti IGF-1 transfected T98G cells cultured in serum-free medium plus 50 uM Zn2+.
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ABCB2 p.Thr98Gly 23526983:298:51
status: NEW313 A, Expression of TAP-1 peptide in T98G cells was down-regulated by addition of IGF-1 to culture medium.
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ABCB2 p.Thr98Gly 23526983:313:34
status: NEW315 Lanes 1 and 2 are NT cells from the T98G and HG-2 cell lines respectively. Lane 3 and lane 4 are T98G TX (clone b) and HG-2 TX (clone 5), respectively, into which IGF-1 was added overnight.
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ABCB2 p.Thr98Gly 23526983:315:36
status: NEWX
ABCB2 p.Thr98Gly 23526983:315:97
status: NEW318 The expression of TAP-1 was examined as a function of time following addition of IGF-1 (100 ng/ml) in TX T98G cells in absence of serum and in the presence of Zn2+.
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ABCB2 p.Thr98Gly 23526983:318:105
status: NEW