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

Tumors of the central nervous system account for approximately 9% of all primary neoplasm in humans, while tumors of covering elements, the meninges, account for 13-19% and constitute the second largest group of brain tumors. These are known to exhibit a variety of chromosomal abnormalities besides change in the expression level of certain oncogenes. Among oncogenes, bcl2, an anti-apoptotic factor and ROS1 that encodes a protein with a structure similar to the epidermal growth factor (EGF) and insulin receptor and has a tyrosine kinase activity, have been shown to be associated with many malignant tumors. In the present study we have analysed the expression of bcl2 using immuno-histochemistry and ROS1 expression by reverse-transcription coupled with polymerase chain reaction (RT-PCR) of the transcript using primers specific for the intra-cellular domain and then tried to correlate the findings with the subtype of the meningioma defined on the basis of histology. Out of the six bcl2 positive cases in our study, there were three transitional tumors, two fibroblastic and one recurrent meningioma subtype. bcl2 seemed to be more consistently expressed in the cytoplasm of spindle cell component of meningiomas. Thirteen meningiothelial meningiomas did not show any staining for bcl2. ROS1 gene expression could be detected in 4 tumors all of those were Grade-I meningothelial meningiomas. One of the malignant meningioma included in the study was clearly negative for bcl2 as well as ROS1. Thus bcl2 and ROS1 oncogene expression in meningiomas are not concurrent and neither can be ascribed to any histologic subtype or grade of tumor.
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PMID:Bcl2 and ROS1 expression in human meningiomas: an analysis with respect to histological subtype. 1676 43

Astrocyte elevated gene-1 (AEG-1) has recently been proposed to be involved in tumor development, invasion, and metastasis in several human cancers. However, the functional importance of AEG-1 expression in human meningioma has not been determined. We investigate the level of AEG-1 expression by quantitative reverse transcription PCR, immunohistochemistry analysis, and western blotting in various human meningioma tissues and cells. To determine the suppressive effect of AEG-1 on meningioma progression, we inhibited AEG-1 expression using small interfering RNA and examined cell proliferation, apoptosis, colony formation and tumorigenicity in a mouse xenograft model. AEG-1 expression was frequently elevated at both mRNA and protein levels in meningioma tumor tissues and in meningioma-derived cells as well. This elevation was more commonly observed in high-grade tumors than in benign ones. The knockdown of AEG-1 led to a decrease in overall cell proliferation, as well as anchorage-independent growth of malignant meningioma. In addition, apoptotic cell death occurred in AEG-1 depleted meningioma cells through p-Akt and Bcl-2 suppression. Furthermore, a mouse xenograft meningioma model showed that inhibition of AEG-1 expression significantly decreased tumor growth. Altogether, these data show that the elevation of AEG-1 contributes to the malignant progression of meningiomas, suggesting that AEG-1 could be a novel therapeutic target against human meningiomas.
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PMID:Expression of astrocyte elevated gene-1 (AEG-1) in human meningiomas and its roles in cell proliferation and survival. 2518 4

The GTPase-activating protein RLIP76 is overexpressed in and correlates with the pathological grade of many malignant tumor cells. But the potential correlation between RLIP76 and clinical outcomes in patients with meningioma remains unknown. In this study, we examined the expression of RLIP76 in meningioma and correlated the RLIP76 expression to the patient outcome. RLIP76 expression in tumor tissues was examined with immunohistochemistry, quantitative reverse-transcription polymerase chain reaction(RT-PCR) and Western-blot. Immunohistochemistry showed an increased RLIP76 immunostaining score in anaplastic and atypical meningiomas versus classical meningiomas. Statistical analyses revealed that RLIP76 immunostaining positively correlated with immunostaining for Ki-67, a nuclear protein highly expressed in proliferating cells(r=0.29, p=0.034 by Spearman's correlation coefficient). Clinicopathological evaluation suggested that RLIP76 expression be associated with tumor grade and recurrence(P<0.05). Univariate and Cox analysis indicated that RLIP76 was an independent prognostic factor for tumor recurrence. Furthermore, the human malignant meningioma cell lines IOMM-Lee and CH157-MN stably transfected with short hairpin RNA (siRNA) targeting RLIP76 were then examined by in vitro growth assays, and apoptosis assays. RLIP76 knockdown in IOMM-Lee and CH157-MN cells inhibited cell proliferation and induced apoptosis. Western blot analysis revealed that cells underexpressing RLIP76 exhibited decreased B-cell lymphoma-2(Bcl-2) expression but increased apoptosis effector caspase-3 expression. These findings demonstrate that high RLIP76 expression is associated with a poor outcome of meningioma and may provide a new gene therapy approach for patients with malignant meningiomas.
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PMID:Overexpression of RLIP76 Required for Proliferation in Meningioma Is Associated with Recurrence. 2599 41