Ets‐1 is up‐regulated together with its target gene products matrix metalloproteinase‐2 and matrix metalloproteinase‐9 in atypical and anaplastic meningiomas

Okuducu, Ali Fuat; Zils, Ulrich; Michaelis, S. A. M.; Michaelides, Stylianos A.; Deimling, Andreas von

doi:10.1111/j.1365-2559.2006.02432.x

Cited by 27 publications

(17 citation statements)

References 36 publications

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“…Hypoxia has been shown to induce Ets-1 via the activity of HIF-1α [19]; therefore, we surmise that Ets-1 could be involved in the signalling cascade, terminating in MMP up-regulation observed in our hypoxia studies. More recently, MMP-2 and MMP-9 were found to be target genes for Ets-1 [33]. …”

Section: Discussionmentioning

confidence: 99%

Hypoxia in Abdominal Aortic Aneurysm Supports a Role for HIF-1α and Ets-1 as Drivers of Matrix Metalloproteinase Upregulation in Human Aortic Smooth Muscle Cells

et al. 2010

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Background/Aims: We sought to determine whether hypoxia is an initiating factor in the matrix metalloproteinase-2 (MMP-2) up-regulation observed in abdominal aortic aneurysm (AAA) and whether hypoxia-inducible factor-1α (HIF-1α) or Ets-1 are mediating factors. Methods: Human AAA and normal aorta were analysed for MMP-2, HIF-1α and Ets-1 by immunohistochemistry. Human aortic smooth muscle cell (HASMC) cultures exposed to experimental hypoxia were analysed for hypoxia-induced proteins using gelatin zymography and immunoblotting. Multiplex PCR was used to detect MMP-1, membrane-type (MT)-MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9. Results: AAA tissues expressed HIF-1α, MMP-2 and Ets-1 strongly within smooth muscle cells and inflammatory infiltrate of the tunica media. Up-regulated MMP-2 was detected in hypoxia-exposed HASMC (p < 0.05), with MMP-9 elevations after exposure to sequential O₂ decreases (p < 0.05). Immunoblotting confirmed HIF-1α, Ets-1, VEGF and MMP-2 are up-regulated in HASMC exposed to hypoxia (p < 0.05), while transcription for MMP-1, MT-MMP-1, MMP-9, MMP-2 and MMP-7 (p < 0.05) increased in hypoxic HASMCs. Conclusion: Hypoxia facilitates HIF-1α, Ets-1 and VEGF up-regulation in addition to driving enhanced secretion of MMP-2 and MMP-9 by HASMC. Enhanced transcription of factors relevant to aneurysmal disease in hypoxia indicates possible roles in disease progression and potential targets for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Hypoxia in Abdominal Aortic Aneurysm Supports a Role for HIF-1α and Ets-1 as Drivers of Matrix Metalloproteinase Upregulation in Human Aortic Smooth Muscle Cells

et al. 2010

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“…The studies on tumor invasion and recurrence are focused on MMP-2 and MMP-9. MMP-2 expression is particularly observed in grade 2 and 3 meningiomas (16). There is a clear relationship between MMP-2 expression and tumor recurrence in meningiomas.…”

Section: Efendioglu M Et Al: Mmp-1 Gene Promoter Region In Invasion mentioning

confidence: 87%

The role of a single nucleotide polymorphism of the matrix metalloproteinase-1 gene promoter region in invasion and prognosis of meningiomas

Efendioğlu

Başaran²,

Bayrak³

et al. 2014

Turkish Neurosurgery

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AIm:The matrix metalloproteinase (MMP) enzyme family has been shown to be active in tumorigenesis and tumor progression. In this study, we analyzed the prevalence of a guanine insertion in the MMP-1 gene promoter region in meningiomas and its effect on invasion and prognosis. mATERIAL and mETHods:The study was performed with 33 meningioma patients. We also included 33 healthy patients in the study as a control group. The promoter area was amplified by polymerase chain reaction (PCR) following DNA isolation. The polymorphism was detected by restriction fragment length polymorphism (RFLP). REsuLTs:According to the WHO classification of meningiomas, 87.9% of the affected patients were grade 1, and 12.1% were grade 2. In total, 72.7% of the meningioma patients (n=24) had at least one copy of the insertion (2G/1G or 2G/2G genotypes) and 27.3% (n=9) did not (1G/1G). There was no significant difference between the meningioma and control groups according to genotype distribution. CoNCLusIoN:In this study, the polymorphism in the matrix metalloproteinase-1 gene promoter region did not have an effect on the initiation, growth and progression of meningioma.KEywoRds: Meningioma, Single nucleotide polymorphism, SNP, MMP-1, Interstitial collagenase, Matrix metalloproteinase ÖZ AmAÇ: Matriks metalloproteinaz (MMP) enzim ailesinin tümör oluşumu ve progresyonunda etkili olduğu gösterilmiştir. Bu çalışmada menenjiyomlarda matriks metalloproteinaz-1 geni promotor bölgesine guanin insersiyonunun prevalansı ve bunun invazyona ve prognoza etkisi araştırıldı. yÖNTEm ve GEREÇLER: Çalışma 33 tane menenjiyomlu hasta ile yapıldı. Aynı zamanda 33 tane sağlıklı kişi de çalışmaya kontrol grubu olarak dahil edildi. DNA izolasyonundan sonra promotor bölge polimeraz zincir reaksiyonu ile çoğaltıldı. Polimorfizm, restriksiyon fragman uzunluk polimorfizmi ile tesbit edildi.BuLGuLAR: Dünya Sağlık Örgütü (DSÖ) sınıflamasına göre hastaların %87,9'unda derece I, %12,1'inde derece II menenjiyoma saptandı. Menenjiyomlu hastaların %72,7'si (n=24) en az bir tane guanin insersiyonuna sahipti (2G/1G or 2G/2G genotipleri), ve %27,3' ü (n=9) sahip değildi (1G/1G). Genotip dağılımına göre menenjiyomlarla kontrol grubu arasında bir fark yoktu. soNuÇ: Bu çalışmada menenjiyomlarda matriks metalloproteinaz-1 geni promotor bölgesindeki polimorfizmin, menenjiyomların başlamasına-büyümesine ve ilerlemesine etki etmediği izlenmiştir.ANAHTAR sÖZCÜKLER: Menenjiyom, Tek nükleotid polimorfizmi, SNP, MMP-1, Matriks metalloproteinaz, İnterstisyel kollajenaz

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“…found that Ets-1 downregulated VEGF expression in endothelial cells, suggesting that the VEGF production by endothelial cells is regulated by Ets-1. Also, Ets-1 has been identifi ed as eff ectors of many signalling pathways, such as MAPK/ERK signalling pathway (Paumelle et al 2002;Wasylyk et al 1998) Okuducu et al 2006;Park et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Ets-1 regulates its target genes mainly by DNA methylation in human ovarian cancer

Wan

Peng

Guan

2013

Journal of Obstetrics and Gynaecology

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Ovarian cancer is the second most common gynaecological cancer worldwide, and its molecular mechanism has not been completely understood. Ets-1 is a member of the Ets transcription family and can play important roles in the regulation of extracellular matrix remodelling, invasion, angiogenesis and drug resistance in several malignancies, including ovarian cancer. In the current study, we downloaded two datasets from Gene Expression Omnibus database and sought to explore the regulation mechanism of Ets-1 in ovarian cancer by computational analysis of gene expression profiles. Microarray analysis identified a total of 548 genes that were regulated by Ets-1 in ovarian cancer. Functional annotation of these genes revealed that Ets-1 may be involved in several biological processes, both physiological and pathological, such as system development, response to stimulus, vascular endothelial growth factor (VEGF) production, morphogenesis, cell proliferation, cell adhesion and signal transduction. Further, DNA methylation analysis of the DEGs found that 26.5% (145) of them were differentially methylated genes in ovarian cancer. Our results provide insight into the mechanism of Ets-1 regulating the transcription of its target genes in the complex and multistep process of ovarian cancer progression.

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Ets‐1 is up‐regulated together with its target gene products matrix metalloproteinase‐2 and matrix metalloproteinase‐9 in atypical and anaplastic meningiomas

Abstract: Ets-1 may be involved in the transcriptional regulation of MMP-2 and MMP-9 as well as in the invasive process in meningiomas. Evaluation of these expressions might be of prognostic value for meningiomas.

Cited by 27 publications

References 36 publications

Hypoxia in Abdominal Aortic Aneurysm Supports a Role for HIF-1α and Ets-1 as Drivers of Matrix Metalloproteinase Upregulation in Human Aortic Smooth Muscle Cells

Hypoxia in Abdominal Aortic Aneurysm Supports a Role for HIF-1α and Ets-1 as Drivers of Matrix Metalloproteinase Upregulation in Human Aortic Smooth Muscle Cells

The role of a single nucleotide polymorphism of the matrix metalloproteinase-1 gene promoter region in invasion and prognosis of meningiomas

Ets-1 regulates its target genes mainly by DNA methylation in human ovarian cancer

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