Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe here the establishment of a new synovial sarcoma cell line, SYO-1, derived from a biphasic synovial sarcoma that developed in the groin of a 19-year-old female. The cell line was maintained for more than 70 passages (more than 24 months) in vitro. The SYO-1 cells in monolayer culture exhibited a spindle shape without conspicuous pleomorphism. Immunohistochemically, the cells were positive for vimentin, type IV collagen, S-100, mdm2, bcl-2, c-Met and c-Kit. Tumors developed by their implantation in nude mice histologically showed biphasic features that were composed of areas of fascicles of spindle cells and areas of compact proliferation of polygonal to ovoid cells, which occasionally formed epithelial plaque and expressed cytokeratin and EMA. SYO-1 cells harbored the characteristic t(X;18)(p11.2;q11.2) translocation by chromosome analysis and SYT-SSX2 chimeric transcript by RT-PCR. The SYO-1 cells, the first characterized cell line derived from biphasic synovial sarcoma retaining the characteristic genetic and phenotypic features of the tumor, will be useful for various investigations on synovial sarcoma, especially for its epithelial differentiation.
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PMID:Establishment and characterization of a biphasic synovial sarcoma cell line, SYO-1. 1474 40

The purpose of the present study was to investigate the level of apoptosis and expressions of p53, mdm2 and bcl-2 proteins in salivary gland adenoid cystic carcinoma (ACC) to determine potential relationships among apoptosis, apoptosis-associated proteins and clinical cumulative survival. Thirty-nine formalin-fixed, paraffin-embedded cases, cribriform (17), tubular (13) and solid (9), were studied by immunohistochemistry. Apoptosis detection and analysis were determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). There was an inverse significance between the apoptotic index (AI) and bcl-2 expression (P = 0.018), whereas no correlation was found between the AI and either p53 or mdm2 expression (P = 0.416 and P = 0.456). Co-expression of p53 and mdm2 was found in 22 cases (P = 0.037). Patients with p53-positive tumors had a worse prognosis than those with p53-negative tumors (P = 0.014). Patients with a high AI had a better cumulative survival than patients with a low AI (P = 0.038). The present study suggests that p53 expression and AI can be useful as prognostic values; bcl-2 protein plays a role in the down-regulation of apoptosis and is also potentially useful as a prognostic parameter in salivary gland ACC.
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PMID:Prognostic value of apoptosis and apoptosis-associated proteins in salivary gland adenoid cystic carcinoma. 1502 21

Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.
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PMID:Gene expression profiling of p53(+/-) knockout and wild-type mice following diethylstilbestrol administration. 1554 18

In Argentina, lymphomas account for 13.6% of all pediatric tumors and 47% of them are Hodgkin lymphoma. Previous studies of lymphoma series have reported the expression of apoptotic and cell cycle proteins. Our aim was to study these markers in our pediatric patients and correlate them with their outcome. Immunohistochemical staining with monoclonal antibodies anti-p53, bcl-2, p21, and mdm2 were performed on formalin-fixed paraffin-embedded Hodgkin lymphoma lymph node biopsies from 54 pediatric patients. The analyzed oncogenes p53, bcl-2, p21, and mdm2 exhibited 81%, 44%, 76%, and 90% positive staining, respectively. The most prevalent p53/p21 expression pattern was p53+/p21+, in 57% of cases, whereas concerning p53/mdm2 expression pattern p53+/mdm2+ was observed in 61% of cases. We failed to find any statistically significant correlation between oncogene expression and patient's survival. It seems that p53 plays an important role in lymphomagenesis in our studied population, because it is overexpressed in 81% of Hodgkin lymphoma cases and in more than 50% of cases, it might be able to activate its cellular effectors. Bcl-2 staining observed in 44% of our cases could represent a failure in bcl-2 down-regulation that leads to a rescue event in defective germinal center B-cells, that allows them to develop into Reed-Sternberg and Hodgkin cells.
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PMID:No Influence of bcl-2, p53, and p21waf1 protein expression on the outcome of pediatric Hodgkin lymphomas. 1700 59

The aim of this study was to understand the mode of action of tea polyphenol epigallocatechin gallate (EGCG) in vivo. Swiss albino mice were treated i.p. with EGCG at two different doses i.e. 12-mg/kg body weight and 15-mg/kg body weight, for 7 days prior to inoculation of Sarcoma180 (S180) cells and continued for another 7 days. The growth of the S180, harvested 7 days after inoculation, was significantly reduced due to treatment with EGCG. The flowcytometric analysis of S180 cells, showed significant increase in apoptosis and reduction in the number of cells in G2/M phase of cell cycle due to treatment with EGCG. The induction of apoptosis has also been confirmed by the TUNEL and DNA fragmentation assays. Both RT-PCR and Western blot analysis showed significant up-regulation of p53 and bax, and down-regulation of bcl-2 and c-myc due to EGCG treatment. No changes in the expression pattern of p21, p27, bcl-xl, mdm2 and cyclin D1 were seen. Interestingly, there was significant down-regulation of spliceosomal uridylic acid rich small nuclear RNAs (UsnRNAs) U1B and U4-U6 due to EGCG treatment. This indicates that these UsnRNAs may be involved in the apoptosis process. Taken together, our study suggests that in vivo EGCG could induce apoptosis in S180 cells through alteration in G2/M phase of the cell cycle by up-regulation of p53, bax and down-regulation of c-myc, bcl-2 and U1B, U4-U6 UsnRNAs.
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PMID:Epigallocatechin gallate induced apoptosis in Sarcoma180 cells in vivo: mediated by p53 pathway and inhibition in U1B, U4-U6 UsnRNAs expression. 1704 54

Epithelial ovarian carcinoma is worldwide the sixth most common female cancer, and this malignancy carries the highest mortality among all gynecological cancers. The high mortality is due mostly to the fact that the tumor is frequently diagnosed late, in advanced stage, as the early disease is often asymptomatic and no effective screening methods are available. The most important prognostic factors in ovarian carcinoma are the stage, size of residual tumor following surgery, presence of ascites, age and the general condition of the patient, tumor histology, and, in patients with early disease, also the grade of the tumor. Large number of studies on prognostic and predictive factors in epithelial ovarian carcinoma has been published, often with contradictory results. The most intensely studied prognostic factors are those for expression of hormonal receptors, for tumor proliferation activity (mainly by antigen Ki-67 and topoisomerase IIalpha), the markers of apoptosis (p53, p21, mdm2, bcl-2 and other proteins), or other oncoproteins (particularly HER-2/neu).
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PMID:Contribution of immunohistochemistry in prognostic assessment of epithelial ovarian carcinoma --review of the literature I. 1711 4

Cholinergic cell lines were established by fusion of embryonic day 17 wild-type neurons from rat basal forebrain (BF) and upper brainstem (BS) with N18tg neuroblastoma cells. Isolated clones expressed choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS) activities that were increased upon differentiation with retinoic acid. Clones from the BF expressed high levels of the tyrosine kinase type A (TrkA) receptor expression and activation of the mitogen-activated kinase ERK2 upon treatment with nerve growth factor. Like wild-type cholinergic populations, the six clones studied were variably resistant to nitric oxide (NO) excess from addition of S-nitroso-N-acetyl-D, L-penicillamine (SNAP). Of these, the BS2 clone exhibited resistance like in vivo BS cholinergic neurons, while the MS10 clone mimicked in vivo BF vulnerability. Apoptosis in response to NO excess was preceded by increases in mitochondrial responses bax/bcl-2 ratios, but cytochrome C was not released. Mitochondrial levels of apoptosis initiating factor (AIF) were either unchanged or increased, and only in MS clones was endonuclease G (EndoG) released. Microarray data indicated the existence of endoplasmic reticular (ER) stress and caspase-4 and caspase-12 were involved in the pathway to DNA fragmentation. The array data also indicated a survival role for mdm2, and its blockade rendered vulnerable the brainstem survivor clone BS2. Akt and ERK1/2 pathways were activated in response to NO and their blockade increased DNA fragmentation. Blockade of GSK-3 alpha/beta, a downstream target of Akt, reduced SNAP toxicity and this was more prominent in basal forebrain clones. We have identified two cholinergic cell lines useful for molecular studies of cholinergic vulnerability. We hypothesize that, in cholinergic neurons, control of ER stress signaling may be a major factor in differential vulnerability.
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PMID:Establishment of cholinergic neuron-like cell lines with differential vulnerability to nitrosative stress. 1750 6

An imbalance between apoptotic and proliferative processes is believed to underlie colorectal neoplasia. We evaluated the expression of bcl-2, p53, mdm2 proteins, and apoptosis in colorectal neoplasms, as well as their correlation with clinico-pathological parameters, using image analysis. Biopsies from 46 colorectal cancers, 121 adenomas, and 25 controls were studied using monoclonal antibodies against p53, bcl-2, mdm2 and the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) method for apoptosis. P53 and bcl2 protein expression was higher in adenomas >or=1 cm (P < 0.03) and tubulovillous-villous adenomas (P < 0.03), and correlated with dysplasia (P < 0.03). In Cox regression analysis, Dukes' stage was the most significant independent prognostic indicator of a worse survival (P < 0.019), whereas when stage was eliminated, bcl-2 expression was also a powerful predictor for bad prognosis (P = 0.02). In conclusion, both bcl-2 and p53 immunohistochemical profiles may be useful adjuncts in detecting adenomas with a malignant potential, whereas bcl-2 could be used in combination with Dukes' stage as a predictor of prognosis in colorectal cancer.
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PMID:Potential role of apoptosis and apoptotic regulatory proteins in colorectal neoplasia: correlations with clinico-pathological parameters and survival. 1756 77

Low-grade fibromyxoid sarcomas (LGFMS) bear either the t(7,16) (q32-34;p11) or t(11,16) (p11;p11) translocations, resulting in FUS-CREB3L2 or FUS-CREB3L1 fusions, respectively. Heretofore, fusion transcripts were mainly detected in frozen tissues, using reverse transcription-polymerase chain reaction. In this study, we aimed to develop a reliable method to detect these in paraffin-embedded tissues, and to examine the clinicopathologic characteristics of a series of translocation-positive LGFMS. Sixty-three neoplasms with typical morphologic features of LGFMS and 66 non-LGFMS tumors selected for their resemblance to LGFMS (LGFMS-like tumors) were examined. RNA of sufficient quality could be extracted from 111/129 (86%) cases (59 LGFMS, 52 non-LGFMS). Of all, 48/59 (sensitivity, 81%) LGFMS contained detectable transcripts (45 FUS-CREB3L2, 3 FUS-CREB3L1). Most relevant clinicopathologic features of fusion-positive LGFMS included predominance in lower extremities (22/48; thigh: 13/48), deep situation (46/48), and occasional presence of unusual histologic features, for example, hypercellular areas (16/48), foci of epithelioid cells (13/48), and giant rosettes (6/48). Most tumors expressed EMA (41/45), at least focally, CD99 (38/41) and bcl-2 (36/41) while being essentially negative for CD34 (2/45), mdm2 (1/41), smooth muscle actin (1/45), S100 protein (0/46), desmin (0/44), h-caldesmon (0/42), keratins (0/44), and CD117 (0/40). Eleven presumed LGFMS were fusion negative. Of all, 7/52 non-LGMFS neoplasms contained FUS-CREB3L2 transcripts, of which 4 had been diagnosed as sclerosing epithelioid fibrosarcoma. In conclusion, FUS-CREB3L1/L2 fusion transcripts can be detected in paraffin-embedded LGFMS in a sensitive manner, using reverse transcription-polymerase chain reaction. Most fusion-positive LGFMS are EMA-positive and CD34/S100/smooth muscle actin negative. The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related.
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PMID:Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. 1772 Nov 95

Microcystins (MCs) are hepatotoxic cyclic heptapeptides produced by freshwater cyanobacteria. They are inhibitors of serine/threonine protein phosphatases 1A and 2A and are involved in liver tumour promotion. Several recent studies indicated that MCs are genotoxic and may also act as tumour initiators. Based on our previous results showing that microcystin-LR (MCLR) induces DNA damage in HepG2 cells, we have now explored the effect of MCLR on the expression of selected genes known to be involved in the cell response to DNA damage and apoptosis. The HepG2 cells were exposed to non-cytotoxic concentrations (0.01, 0.1 and 1 microg/ml) of MCLR for various periods of time (2-16 h) and the mRNA expression was determined with the quantitative real-time polymerase chain reaction (QRT-PCR). We found a significantly elevated expression of tumour suppressor gene p53 and its downstream-regulated genes involved in DNA repair and cell cycle regulation (p21, gadd 45a, mdm2), as well as increased expression of the pro-apoptotic gene bax, but no alterations of the anti-apoptotic bcl-2. Up-regulation of the expression of mdm2, p21 and gadd45a provides strong support for our previous suggestion that MCLR is a genotoxic carcinogen. The increased ratio of expression of bax to that of bcl-2 induced by MCLR suggests that apoptosis in HepG2 cells proceeds via the mitochondrial pathway.
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PMID:Patterns of microcystin-LR induced alteration of the expression of genes involved in response to DNA damage and apoptosis. 1819 Nov 68


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