Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases. In this study, we evaluated the mRNA expression level of LRIG1-3 in human glioma cell lines and control-matched glioma tissues, characterized the sub-cellular localization of an LRIG3-GFP fusion protein, and analyzed the relationship between sub-cellular localization of LRIG1-3 and clinical parameters in 404 astrocytic tumors by immunohistochemistry. LRIG1-3 mRNA was detected in all human glioma cell lines and matched glioma samples, with large differences in the expression levels. Ectopically expressed LRIG3-GFP localized to perinuclear and cytoplasmic compartments, and to the cell surface of transfected glioma cells. Perinuclear staining of LRIG1-3 was associated with low WHO grade and better survival of the patients. Perinuclear staining of LRIG3 was associated with a lower proliferation index and was in addition to tumor grade, an independent prognostic factor. Furthermore, within the groups of grade III and grade IV tumors, perinuclear staining of LRIG3 significantly correlated with better survival. These results indicate that expression and sub-cellular localization of LRIG1-3 might be of importance in the pathogenesis and prognosis of astrocytic tumors.
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PMID:Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors. 1653 60

LRIG3 (leucine-rich repeats and immunoglobulin-like domains, LRIG) gene is both under-and over-expressed in human cancers and its role on tumor growth is not fully clarified. Here, we used a human U6 promoter-driven DNA template approach to induce short hairpin RNA (shRNA)-triggered RNA interference (RNAi) to block LRIG3 gene expression in the human glioma cell line GL15. Specific knockdown of LRIG3 by shRNA resulted in significantly increase of the GL15 invasion and adhesion activity in vitro and markedly promoted cell growth. LRIG3 repression also induced increment of the proportion of G0/G1 cells and inhibited apoptosis in GL15 cells. Our results demonstrated that RNAi against LRIG3 could effectively down regulate LRIG3 gene expression. LRIG3 might be involved in the regulation of EGFR signaling, and serve as a tumor suppressor gene in the pathogenesis of glioma.
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PMID:Inhibition of LRIG3 gene expression via RNA interference modulates the proliferation, cell cycle, cell apoptosis, adhesion and invasion of glioblastoma cell (GL15). 1920 Jun 47

The effects of RNAi-mediated gene silencing of LRIG3 expression on cell cycle and survival of human glioma cell line GL15 and the possible mechanisms were explored. The plasmids pGenesil2-LRIG3-shRNA1 and pGenesil2-LRIG3-shRNA2 were transfected into GL15 glioma cells respectively by using Metafectine, and the transfected cells that stably suppressed LRIG3 expression were selected by G418. The control cells were transfected with negative control shRNA. The changes in LRIG3 mRNA and protein levels were measured by RT-PCR and Western blot. The apoptosis rate and cell cycle were analyzed by flow cytometry. As compared with the negative shRNA-transfected GL15 cells, LRIG3 mRNA expression in GL15 cells transfected with pGenesil2-LRIG3-shRNA1 and pGenesil2-LRIG3-shRNA2 was silenced by 52.4%, 63.8%, and LRIG3 protein expression was reduced by 50.9% and 67.4% respectively. The LRIG3-specific siRNA transfected cells had higher proliferation rate than control cells. Cell cycle analysis showed that silencing LRIG3 increased the percentage of G(2)/M phase cells and the proliferation index significantly (P<0.01). Silencing LRIG3 could inhibit the apoptosis of GL15 cells (P<0.05). These findings suggest that the siRNA targeting LRIG3 gene shows a dramatic inhibitory effect on RNA transcription and protein expression, then promoting the proliferation of GL15 cells, arresting GL15 cells in G(2)/M phase, and suppressing apoptosis of GL15 cells.
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PMID:Effects of RNAi-mediated gene silencing of LRIG3 expression on cell cycle and survival of glioma cells. 1922 71

Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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PMID:A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk. 2044 91

This study examined the effects of over-expression of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the cell cycle and survival of human glioma cell line U87 and U251 and explored the possible mechanisms. The LRIG3 gene was transduced into U87 and U251 cells respectively by using lentivirus and the transduced cells were selected by puromycin. The changes in LRIG3 mRNA and protein levels were measured by RT-PCR and Western blotting. The apoptosis rate was detected by Annexin V-FITC/PI double labeling and the cell cycle was flow cytometrically analyzed. Compared with control cells, LRIG3 mRNA expression in U251 and U87 cells transduced with pLVX-DsRed-LRIG3-Monomer-N1 were increased by 77.6% and 129.7%, and LRIG3 protein expression was raised by 141.3% and 322.7%, respectively. Cell cycle analysis showed that LRIG3 over-expression increased the percentage of cells at G(0)/G(1) phase (P<0.01). Over-expressed LRIG3 could significantly promote the apoptosis of U87 and U251 cells (P<0.05). These findings suggest that the over-expression of LRIG3 could arrest the cell cycle in G(0)/G(1) phase, and promote apoptosis of U87 and U251 cells.
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PMID:Effect of over-expressed LRIG3 on cell cycle and survival of glioma cells. 2203 58

Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3 gene is mapped to chromosome 12q13.2, a region that is frequently deleted in a subset of glioblastoma multiforme (GBM). It has been reported that perinuclear LRIG3 staining correlated with low WHO grade of glioma and better survival of the patients. However, the relationship between LRIG3 and glioma is not very clear. The purpose of this study is to demonstrate the impacts of LRIG3 on biological characteristics of glioma and its possible mechanisms. We found that transduction of LRIG3 into glioblastoma cells inhibited cell growth in vitro and in vivo, promoted cell apoptosis, and restrained cell invasion and migration. Further studies demonstrated that LRIG3 negatively regulated the epidermal growth factor receptor (EGFR) signaling pathway. Inhibition of EGFR could reduce the effects of LRIG3 knockdown on cell proliferation and EGFR signaling pathway. In conclusion, LRIG3 functions as a tumor suppressor by attenuating EGFR signaling pathway and the restoration of LRIG3 may offer therapeutic potential against malignant gliomas.
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PMID:LRIG3 modulates proliferation, apoptosis and invasion of glioblastoma cells as a potent tumor suppressor. 2570 90

Gliomas are the most common intracranial tumors of the nervous system. These tumors are characterized by unlimited cell proliferation and excessive invasiveness. Despite the advances in diagnostic imaging, microneurosurgical techniques, radiation therapy, and chemotherapy, significant increases in the progression free survival of glioma patients have not been achieved. Improvements in our understanding of the molecular subtypes of gliomas and the underlying alterations in specific signaling pathways may impact both the diagnosis and the treatment strategies for patients with gliomas. Growth factors and their corresponding receptor tyrosine kinases are associated with oncogenesis and development of tumors in numerous human cancer types, including glioma. Leucine-rich repeats and immunoglobulin-like domains (LRIG) are integral membrane proteins which contain three vertebrate members including LRIG1, LRIG2 and LRIG3. They mainly function as regulators of growth factor signaling. Specifically, LRIG1 has been identified as a tumor suppressor in human cancers. In contrast, LRIG2 appears to function as a tumor promoter, while LRIG3 appears to have a function similar to that of LRIG1. In the present review, we summarize the functional roles, molecular mechanisms, and clinical perspectives of LRIG proteins in gliomas and propose that these proteins may be useful in the future as targets for treatment and prognostication in glioma patients.
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PMID:LRIG proteins in glioma: Functional roles, molecular mechanisms, and potential clinical implications. 2924 24