Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human epithermoid carcinoma-derived cell line MA1, established by introduction of the adenovirus E1A 12 S cDNA linked to the mouse mammary tumor virus long terminal repeat, elicits apoptosis after induction of E1A12S in response to dexamethasone. The level of topoisomerase IIalpha begins to decrease steeply within 36 h preceding the onset of DNA fragmentation, whereas its mRNA level is unchanged (Nakajima, T., Ohi, N., Arai, T., Nozaki, N., Kikuchi, A., and Oda, K. (1995) Oncogene 10, 651-662). Topoisomerase IIalpha prepared by immunoprecipitation or extraction of the nuclear matrix was degraded much more efficiently in the S10 extract prepared from MA1 cells treated with dexamethasone for 42 h (the 42-h extract) than in the extract from untreated MA1 cells (the 0-h extract) in an ATP- and ubiquitin-dependent manner. The proteolytic activity for degradation of topoisomerase IIalpha was suppressed specifically by inhibitors for the proteasome and was much reduced in the 42-h extract prepared from MA1-derivative cell lines expressing E1B19k or Bcl-2. The proteolytic activity was lost after fractionation of the 42-h S10 extract into the S70 and P70 fractions by centrifugation at 70,000 x g for 6 h but partially recovered when these fractions were combined. Polyubiquitinated forms of topoisomerase IIalpha could be detected by incubating it in the S70 or S100 extract, which lacks most of the proteasome activity. The ubiquitination activity in S70 prepared from the 42-h extract was 4- to 5-fold higher than that prepared from the 0-h extract. These results suggest that a component(s) in the ubiquitin proteolysis pathway, responsible for ubiquitination and degradation of topoisomerase IIalpha, is activated or induced during the latent phase of E1A-induced apoptosis.
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PMID:Degradation of topoisomerase IIalpha during adenovirus E1A-induced apoptosis is mediated by the activation of the ubiquitin proteolysis system. 879 59

Immunohistochemical expression of p53, Bc12, vimentin, and S100 protein-positive Langerhans cell was evaluated in 50 endometrial carcinomas (6 stage I, 14 stage II, 20 stage III, and 10 stage IV), in an attempt to use these markers as predictors of survival. Monoclonal antibodies to p53, Bcl-2, vimentin, and S100 proteins were applied to paraffin-embedded sections of endometrial adenocarcinoma, using the avidin-biotin peroxidase complex technique (ABC). All 20 patients with stage I and II carcinomas were alive with a mean follow-up of 3 years. Of 30 patients with stage III and IV carcinomas, 13 died of tumor (3-year survival, 57%; SE, 10%), eight were alive with tumor, and nine were alive with no evidence of tumor (mean follow-up, 46 months). Strong p53 positivity was present in 11 carcinomas (22%), including nine high-stage and two low-stage tumors. Bcl-2 positivity was identified in 33 tumors (66%). These tumors were mostly low stage; however, no correlation was found between Bcl-2 expression and prognosis. Vimentin positivity (P < .001), and tumor infiltration by a large number of S100 protein-positive Langerhans cells (P < .05) were associated with low-stage tumors. Vimentin was expressed in 23 carcinomas, including 70% of low-stage tumors and 20% of high-stage tumors. Most high-grade carcinomas were Langerhans cell depleted; most low-grade carcinomas showed >50 S100 protein-positive Langerhans cells/10 high-power fields. Our results indicate that Langerhans cell infiltration and vimentin positivity of tumor cells are favorable prognostic factors in endometrial carcinomas.
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PMID:Prognostic significance of p53, bcl-2, vimentin, and S100 protein-positive Langerhans cells in endometrial carcinoma. 959 68

Amphoterin is a protein enhancing process extension and migration in embryonic neurons and in tumor cells through binding to receptor for advanced glycation end products (RAGE), a multiligand transmembrane receptor. S100 proteins, especially S100B, are abundantly expressed in the nervous system and are suggested to function as cytokines with both neurotrophic and neurotoxic effects. However, the cell surface receptor for the cytokine function of S100B has not been identified. Here we show that two S100 family proteins, S100B and S100A1, activate RAGE in concert with amphoterin inducing neurite outgrowth and activation of transcription factor NF-kappaB. Furthermore, activation of RAGE by amphoterin and S100B promotes cell survival through increased expression of the anti-apoptotic protein Bcl-2. However, whereas nanomolar concentrations of S100B induce trophic effects in RAGE-expressing cells, micromolar concentrations of S100B induce apoptosis in an oxidant-dependent manner. Both trophic and toxic effects are specific for cells expressing full-length RAGE since cells expressing a cytoplasmic domain deletion mutant of RAGE are unresponsive to these stimuli. These findings suggest that activation of RAGE by multiple ligands is able to promote trophic effects whereas hyperactivation of RAGE signaling pathways promotes apoptosis. We suggest that RAGE is a signal-transducing receptor for both trophic and toxic effects of S100B.
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PMID:Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. 1100 87

Using the model of rat sciatic nerve transection and crush injury we studied influence of pyrimidine derivative xymedon on efficacy of regeneration of myelinated axons, number and phenotype of surviving sensory neurons (expressing GAP-43 and Bcl-2) and Schwann cells (S100, GAP-43, PCNA) on the 7th, 15th, 30th, 60th and 90th day after nerve injury. We found out that xymedon counteracts posttraumatic death of sensory neurons, stimulates regeneration of myelinated fibres and proliferation of Schwann cells.
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PMID:[Sensory neurons and Schwann cells during pharmacologic stimulation of the nerve regeneration]. 1121 Apr 58

Spindle cell epitheliomas of the vagina (SCEVs) coexpresses epithelial and mesenchymal markers and were first described as a "mixed tumors of the vagina." However, unlike mixed tumors of other organs, which are believed to originate from myoepithelial cells, SCEVs neither immunohistochemically nor ultrastructurally show features of myoepithelial cells. The present expanded battery of immunohistochemical stains is presented on this rare tumor, including cytokeratin AE1/AE3, CK7, CK20, S100 protein, epithelial membrane antigen, alpha-smooth muscle actin, desmin, CD34, CD99, Bcl-2, vimentin, estrogen and progesterone receptors, and Ki-67. There was minimal expression of alpha-smooth muscle actin and negative staining with S100 protein, with coexpression of cytokeratins and vimentin and expression of estrogen and progesterone receptors, as previously reported in SCEVs. In addition, diffuse expression of CD34, CD99, and Bcl-2 immunohistochemical stains was found, which has not previously been reported. The coexpression of CD34, CD99, and Bcl-2 in SCEVs is consistent with its origin from a primitive/progenitor cell population.
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PMID:Spindle cell epithelioma of the vagina shows immunohistochemical staining supporting its origin from a primitive/progenitor cell population. 1126 Jun 35

P11, a member of the S100 family of calcium-binding proteins, has been shown to interact with BAD (Bcl-xL/Bcl-2-associated death promoter) in the yeast two-hybrid protein-protein interaction assay. Because overexpression of P11 dampens the proapoptotic activity of BAD in transfected cells, we tested the possibility that the expression of this antiapoptotic protein may be regulated by gonadotropins and other survival factors in the ovary. Northern blot analysis of ovaries obtained from prepubertal rats revealed an increased expression of P11 messenger RNA (mRNA) during prepubertal development in the theca cells of preantral and early antral follicles. Treatment of immature rats with PMSG did not affect P11 expression, whereas treatment of PMSG-primed rats with an ovulatory dose of human (h)CG stimulated ovarian P11 mRNA within 6-9 h in the granulosa cells of preovulatory follicles. Treatment of cultured preovulatory follicles in vitro with LH further confirmed the time-dependent stimulation of P11 by gonadotropins. In addition, treatment of cultured preovulatory follicles with MDL-12,330A, an inhibitor of adenylate cyclase, inhibited LH-stimulated P11 mRNA, whereas treatment with forskolin, an adenylate cyclase activator, but not the protein kinase C activator, 2-O-tetradecanol-phorbal-13-acetate, mimicked the LH action, suggesting the role of adenylate cyclase activation in P11 expression. Treatment with other follicle survival factors, including the epidermal growth factor, the basic fibroblast growth factor, and interleukin-1beta, could also stimulate P11 expression in cultured preovulatory follicles. These results demonstrate the expression of P11 mRNA in theca cells of different-sized follicles and in granulosa cells of preovulatory follicles following gonadotropin stimulation, and suggest that P11 may mediate, at least partially, the survival action of gonadotropins during the ovulatory process.
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PMID:Expression of messenger ribonucleic acid for the antiapoptosis gene P11 in the rat ovary: gonadotropin stimulation in granulosa cells of preovulatory follicles. 1135 77

Medulloblastomas occurring in children represent a histological spectrum of varying anaplasia and nodularity. In order to determine whether immunohistochemical markers might be useful parameters in subclassifying these tumors, 17 pediatric medulloblastomas, including nine diffuse/non-anaplastic, four diffuse/anaplastic, three nodular/non-anaplastic and one nodular/anaplastic subtypes, were studied. In the present report, we investigate the expression of neural cell adhesion molecule (NCAM), nerve growth factor receptor (NGFR), neurofilament (NF), synaptophysin (SYN), glial fibrillary acidic protein (GFAP), S100, Bcl-2, and Ki-67 by using the immunohistochemistry against specific antibodies. This study showed that NGFR, NF, GFAP and S100 were not detected in anaplastic subtypes of medulloblastomas (0/5), while non-anaplastic subtypes were mainly expressed within the nodules. All 17 tumors were reactive for NCAM, SYN and Bcl-2. In addition, Ki-67 labeling indices for anaplastic subtypes (39.0 +/- 7.42%) were significantly higher than that of non-anaplastic medulloblastomas (11.4 +/- 8.04%; P < 0.0001). These results suggest that immunohistochemical markers are a useful adjunct in characterizing subtypes of pediatric medulloblastomas.
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PMID:Immunohistochemical analysis for histopathological subtypes in pediatric medulloblastomas. 1258 33

We report a case of solitary fibrous tumor involving the spinal nerve root at the L1-L2 level in a 67-year-old man. The patient presented with lumbar pain and weakness in his right lower extremity. Histologically, the tumor was composed of a proliferation of monomorphous spindle cells in an abundant collagenous stroma; neither necrosis nor mitoses were evident. These cells were strongly immunoreactive with CD34, Bcl-2, CD99, and vimentin, but were negative with S100 protein, smooth muscle actin, and epithelial membrane antigen. Such an immunohistochemical profile was consistent with a solitary fibrous tumor of the spinal nerve rootlet and ruled out the main differential diagnoses, schwannoma and meningioma. The present case suggests that solitary fibrous tumor should be considered in differentiating spindle cell lesions of the spinal cord and nerve rootlet.
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PMID:Solitary fibrous tumor of the spinal nerve rootlet: report of a case mimicking schwannoma. 1498 50

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.
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PMID:Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature. 1516 28

The diagnosis of pediatric tumors relies heavily on immunohistochemical staining of small tissue biopsies, since many entities share a "small blue cell" phenotype. More recently, molecular genetic analysis for detection of specific gene fusion products has become available. With the increased use of such molecular techniques, the authors have noted that tumors with proven molecular diagnoses can exhibit unusual patterns of immunohistochemical staining. This study examines pediatric tumors with a "small blue cell" phenotype in which molecular diagnoses were available where applicable. A panel of immunohistochemical stains was performed (S100, CD56, NB84, CD99 [MIC2], Bcl-2, CD117, CD34, desmin, MNF116, and WT1). In the 370 sections from 37 cases, all primitive neuroectodermal tumors, with and without the presence of t(11;22), demonstrated uniform membranous membrane staining with CD99 (MIC2) and focal staining with CD56, NB84, MNF116, and WT1. All rhabdomyosarcomas, both alveolar and embryonal, demonstrated uniform desmin, CD56, and cytoplasmic WT1 immunostaining. Desmoplastic small round cell tumors showed positive cytokeratin staining, with half having "dot-like" cytoplasmic desmin and WT1 positivity; some showed focal positivity for NB84, CD99, and Bcl-2. The "undifferentiated" sarcomas showed the widest range of staining, with no marker staining all cases. Neuroblastomas exhibited uniform strong staining for CD56 and NB84 and marked cytoplasmic Bcl-2 positivity, and some cases showed cytoplasmic WT1 expression. Blastematous Wilms' tumors showed uniform strong membranous staining for CD56, uniform cytoplasmic staining for Bcl-2, and nuclear expression of WT1. Embryonal pediatric malignancies can demonstrate apparently nonspecific expression patterns for several antigens, which may reflect developmental immaturity rather than specific differentiation pathways.
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PMID:Immunohistochemical findings in embryonal small round cell tumors with molecular diagnostic confirmation. 1572 86


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