IGF-II promoter methylation and ovarian cancer prognosis

Beeghly, Alicia; Katsaros, Dionyssios; Wiley, Andrew; Longrais, Irene A. Rigault de la; Prescott, Anna T.; Chen, H.; Puopolo, Manuela; Rutherford, Thomas J.; Yu, Herbert

doi:10.1007/s00432-007-0211-3

Cited by 11 publications

(13 citation statements)

References 46 publications

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“…Methylation-specific PCR and bisulphite sequencing analysis of IGF2 promoter regions Genomic DNA from tumour and normal liver samples was treated with sodium bisulphite (Herman et al, 1996), and the methylation status of the P2 -P4 promoter regions of IGF2 was analysed by methylation-specific PCR (MSP), as described earlier (Beeghly et al, 2007). Polymerase chain reaction products were run on 2% agarose gels and visualised after staining with ethidium bromide.…”

Section: Loh Analysis Of Igf2mentioning

confidence: 99%

Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma

Honda

Arai²,

Haruta

et al. 2008

Br J Cancer

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IGF2, a maternally imprinted foetal growth factor gene, is implicated in many childhood tumours including hepatoblastoma (HB); however, the genetic and epigenetic alterations have not comprehensively been studied. We analysed the methylation status of the H19 differentially methylated region (DMR), loss of heterozygosity (LOH) and allelic expression of IGF2 in 54 HB tumours, and found that 12 tumours (22%) with LOH, 9 (17%) with loss of imprinting (LOI) and 33 (61%) with retention of imprinting (ROI). Biallelic and monoallelic IGF2 expressions correlated with hypermethylation and normal methylation of H19 DMR, respectively, in two tumours with LOI and seven tumours with ROI. Quantitative RT -PCR analysis showed minimal expression of H19 mRNA and substantial expression of IGF2 mRNA in tumours with LOH or LOI, and substantial expression of both H19 and IGF2 mRNAs in tumours with ROI. Increased IGF2 expression with predominant embryonic P3 transcript was found in the majority of HBs with ROI and foetal livers. In contrast to the earlier reports, our findings suggest that the disruption of the enhancer competition model reported in Wilms' tumour may also occur in HB. Both frequencies of LOH and LOI seem to be lower in HB than in Wilms' tumour, reflecting the different tissue origins.

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Section: Loh Analysis Of Igf2mentioning

confidence: 99%

Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma

Honda

Arai²,

Haruta

et al. 2008

Br J Cancer

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“…Exons 8 to 10 encode the mature protein, thus each transcript generates the same IGF-II peptide [162]. However the four promoters (under control of different transcription factors), and six transcripts (with varying 5' untranslated regions, translatability and stability), regulate the spatial, temporal and level of protein expression [177]. IGF-II is induced by hypoxia in HepG2 human hepatoma cells via its P3 promoter, upregulation of the transcription factor Egr-1 and enhanced binding of Egr-1 to the IGF-II promoter [176].…”

Section: Insulin-like Growth Factors (Igf)mentioning

confidence: 99%

Transcriptional Regulation of Inflammatory Genes Associated with Severe Asthma

Clifford¹,

Coward²,

Knox³

et al. 2011

Current Pharmaceutical Design

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The 10% of patients with the most severe asthma are responsible for a large part of healthcare expenditure and morbidity. Understanding the processes involved is key if new therapeutic approaches are to be developed. Evidence is accumulating that chronic diseases such as asthma are associated with temporal and spatial alterations in the pattern of inflammatory gene expression within the airways. Expression of these genes can be regulated by transcriptional, posttranscriptional, translational and epigenetic mechanisms. It is well established that binding of activated transcription factors to specific inducible gene promoter sites is tightly controlled by chromatin state as a result of histone modifications, particularly the balance between histone acetylation and deacetylation [1]. The interaction between transcription factors and the promoter is key to the diversification of gene expression in a time dependent manner leading to altered gene expression profiles. Alterations of the accessibility of transcription factors to the DNA can have residing effects upon gene transcription. This review will focus on the regulation of several groups of key genes which are involved in chronic airway inflammation and remodelling in asthma drawing mainly from our experience of studying these processes in airway smooth muscle cells. An overview is shown in figure 1.

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“…HTX embryos expressed less (<1 fold) Igf2 than the controls; apparently this difference does not affect embryo size. This suggests that other Igf2 regulating elements such as the Igf2 promoter [Beeghly et al 2007] may also be required to differentially regulate the HVPX and HTX groups.…”

Section: Asg Secretion and Imprinted Gene Expression In Embryosmentioning

confidence: 99%

A Lack of Contact of Sperm with Accessory Sex Gland Secretions Deregulates DNA Methylation and Imprinted Gene Expression in Rodent Embryos

Poon

Lee

Wong

2009

Systems Biology in Reproductive Medicine

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Increased oxidative DNA damage is observed in sperm devoid of contact with accessory sex gland (ASG) secretion. After fertilization, these sperm may produce abnormal embryos. In this study, we investigated the possibility that the pattern of DNA methylation and imprinted gene expression in these embryos may be perturbed. Epididymal sperm, uterine sperm, and embryonic day 13 (E13) embryos were collected from hamster and mouse. The extent of global DNA methylation was determined with an antibody against methylcytosine using an embryo DNA dot. The sperm and embryo Gtl2 promoter and H19 differential methylated region (DMR) were subject to bisulfite sequencing. Expression of their reciprocally activated genes Dlk1 and Igf2 was quantified by real-time PCR. Genome-wide DNA hypomethylation in both hamster and mouse embryos sired by males without ASG was observed. The imprinting pattern of fetal mouse Gtl2 promoter and fetal hamster H19 DMR were also disrupted while the expression of Dlk1 and Igf2 was dysregulated in the hamster embryo. This study suggests that a lack of contact of sperm with the ASG secretion disrupts genomewide DNA methylation and also affects the DNA methylation pattern of imprinted genes in embryos.

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IGF-II promoter methylation and ovarian cancer prognosis

Abstract: This study shows that methylation varies among three IGF-II promoters in ovarian cancer and that this variation seems to have biologic implications as it relates to clinical features and prognosis of the disease.

Cited by 11 publications

References 46 publications

Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma

Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma

Transcriptional Regulation of Inflammatory Genes Associated with Severe Asthma

A Lack of Contact of Sperm with Accessory Sex Gland Secretions Deregulates DNA Methylation and Imprinted Gene Expression in Rodent Embryos

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