Loss of inhibitor of growth (ING-4) is implicated in the pathogenesis and progression of human astrocytomas
| Autor: | George Gatzounis, Maria Repanti, Helen Papadaki, Ekaterini Parassi, Dionysios J. Papachristou, G Klironomos, John Varakis, Vasiliki Bravou |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Tumor suppressor gene Adolescent Protein subunit Cell Cycle Proteins Biology Astrocytoma Pathology and Forensic Medicine Pathogenesis Cohort Studies chemistry.chemical_compound Young Adult medicine Humans Child Gene Transcription factor Research Articles Aged Aged 80 and over Cell Nucleus Homeodomain Proteins Urokinase Plasminogen Activator Brain Neoplasms General Neuroscience Tumor Suppressor Proteins NF-kappa B Brain NF-κB Middle Aged medicine.disease Urokinase-Type Plasminogen Activator chemistry Matrix Metalloproteinase 9 Cancer research Disease Progression Matrix Metalloproteinase 2 Female Neurology (clinical) |
| Zdroj: | Brain Pathol |
| ISSN: | 1750-3639 |
| Popis: | Inhibitor of growth 4 (ING-4) is a tumor suppressor gene that interacts with nuclear factor-kappaB (NF-kappaB) and represses its transcriptional activity. Several lines of evidence suggest that the tumor suppressor gene ING-4, the transcription factor NF-kappaB and its target genes matrix metalloproteases MMP-2, MMP-9 and urokinase plasminogen activator (u-PA) are critically involved in tumor invasion. The aim of the present study was to investigate immunohistochemically the expression pattern of ING-4, NF-kappaB and the NF-kappaB downstream targets MMP-2, MMP-9 and u-PA in human astrocytomas from 101 patients. We found that ING-4 expression was significantly decreased in astrocytomas, and ING-4 loss was associated with tumor grade progression. Expression of p65, a NF-kappaB subunit, was significantly higher in grade IV than in grade III and grade I/II tumors, and a statistical significant negative correlation between expression of ING-4 and expression of nuclear p65 was noticed. MMP-9, MMP-2 and u-PA were overexpressed in human astrocytomas. Of note, astrocytomas of advanced histologic grades (grade III, IV) displayed significantly higher expression levels of these proteins compared to tumors of lower grades (grade I, II). Collectively, our data suggest an essential role for ING-4 in human astrocytoma development and progression possibly through regulation of the NF-kappaB-dependent expression of genes involved in tumor invasion. |
| Databáze: | OpenAIRE |
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