DNA methylation, imprinting and cancer

Plass, Christoph; Soloway, Paul D.

doi:10.1038/sj.ejhg.5200768

Cited by 139 publications

(107 citation statements)

References 114 publications

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“…This observation was clearly demonstrated in the present manuscript through bisulfite DNA sequencing and is consistent with the concept that DNA methylation can modulate gene expression. [57][58][59][60] …”

Section: Discussionmentioning

confidence: 99%

Regulation of the H19 imprinting gene expression in human nasopharyngeal carcinoma by methylation

Tang

Goh

et al. 2003

Intl Journal of Cancer

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In East Asia and Singapore, the human nasopharyngeal carcinoma (NPC) presented clinically is mainly of the undifferentiated type. In contrast, the well-differentiated squamous NPC is more commonly detected in the West. To study the potential differences in carcinogenesis between undifferentiated and differentiated human NPC, we employed cDNA microarrays to isolate genes that might be specific for human undifferentiated NPC. One of the genes identified to be specifically upregulated in the undifferentiated human NPC cell line CNE-2 is the human imprinting gene H19. Interestingly, H19 is not expressed in the welldifferentiated human HK1 NPC cells. Northern blot and in situ hybridization analyses also confirmed that the H19 gene is strongly expressed in the undifferentiated CNE-2 human NPC cell line but not in the well-differentiated HK1 human NPC cell line. In situ hybridization and reverse transcriptasepolymerase chain reaction also demonstrated that H19 is specifically expressed in NPC biopsies and not in non-NPC human tissue biopsies. Furthermore, we demonstrated that deregulation of H19 gene expression in the well-differentiated human HK1 NPC cells could be induced by the hypomethylation of CpG sites of the H19 promoter region. Hypermethylation of gene promoter regions might therefore be an important epigenetic event that plays a role in the differentiation of human NPC cells and the transcriptional silencing of imprinted genes.

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Section: Discussionmentioning

confidence: 99%

Regulation of the H19 imprinting gene expression in human nasopharyngeal carcinoma by methylation

Tang

Goh

et al. 2003

Intl Journal of Cancer

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“…This process, so-called "two hits," involves genetic as well as epigenetic mutations. On the other hand, an increasing amount of evidence supports loss of function by methylation in the promoter and/or exon 1 regions (11)(12)(13). Such genes might not accompany a genetic mutation at a very high frequency and thus show a relatively low incidence of deletions, which are needed for mapping the sporadic tumor-related loci with microsatellite markers.…”

Section: Renal Cell Carcinoma (Rcc)mentioning

confidence: 99%

A Novel Ankyrin Repeat-containing Gene (Kank) Located at 9p24 Is a Growth Suppressor of Renal Cell Carcinoma

Sarkar¹,

Roy²,

Hatano³

et al. 2002

Journal of Biological Chemistry

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By a combination of genome subtraction and comprehensive analysis of loss of heterozygosity based on mapping hemizygous deletions for a potential tumor-related locus, a minimum overlapping region of deletions at 9p24 the size of 165 kb was identified and found to harbor a new potential tumor suppressor gene for renal cell carcinoma, the Kank gene. Kank (for kidney ankyrin repeat-containing protein) contains four ankyrin repeats at its C terminus. Expression of the gene was suppressed in 6 of 8 or 6 of 10 cancer tissues examined by reverse transcription-PCR or Western blotting, respectively, and in several kidney tumor cell lines due to methylation at CpG sites in the gene. Epigenetic methylation or imprinting seemed to be the first hit, which was followed by a second hit of deletion, resulting in loss of function in many of these deletion cases. Expression of this gene in expression-negative HEK293 cells induced growth retardation at G 0 /G 1 as well as morphological changes.

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“…Although a strong correlation between promoter methylation and gene silencing has been extensively demonstrated, [35][36][37] the molecular mechanism of this methylation-modulated gene inactivation remains unclear. Among the proposed hypotheses regarding the transcriptional inactivation from promoter methylation, [38][39][40][41][42] one hypothesis that gene repression is induced by a direct influence of methylation on the binding of transcription factors may be related to the results obtained in our study.…”

Section: Aquaporin-5 Expression In Ductal Cells K Motegi Et Almentioning

confidence: 99%

Expression of aquaporin-5 in and fluid secretion from immortalized human salivary gland ductal cells by treatment with 5-aza-2′-deoxycytidine: a possibility for improvement of xerostomia in patients with Sjögren's syndrome

Motegi

Azuma

Tamatani

et al. 2005

Laboratory Investigation

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The aim of the present study was to investigate the possibility that ductal cells, which preferentially survive and/ or proliferate in Sjö gren's syndrome (SS) salivary glands of patients with SS, could acquire the functional expression of membrane water channel aquaporin-5 (AQP5). Thus, in this study, we demonstrate that an immortalized normal human salivary gland ductal cell (NS-SV-DC) line, lacking the expression of AQP5, acquires AQP5 gene expression in response to treatment with 5-aza-2 0 -deoxycytidine (5-Aza-CdR), a DNA demethylating agent. Confocal microscopic analysis revealed the localization of AQP5 expression mainly at the apical and lateral sides of the plasma membrane. The expressed AQP5 protein was functionally active because AQP5 expression resulted in a significant increase in the osmotically directed net fluid rate across monolayers of NS-SV-DC cells. By the analysis of bisulfite sequencing of CpG islands in the AQP5 promoter, hypermethylation within the consensus Sp1-binding sites was commonly observed in parental cell clones, whereas demethylation at the CGs, one in the second consensus Sp1 element and the other outside of the third consensus Sp1 element in the AQP5 promoter, was detected in NS-SV-DC cells after treatment with 5-Aza-CdR. By analyzing the luciferase activity of transfected AQP5 promoter vectors, it became evident that demethylation at the CGs cooperatively functions between these two sites to induce AQP5 expression. Our data, therefore, suggest that treatment of ductal cells with 5-Aza-CdR could result in the expression of the AQP5 gene, thereby leading to increased fluid secretion from ductal cells in SS salivary glands.

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DNA methylation, imprinting and cancer

Cited by 139 publications

References 114 publications

Regulation of the H19 imprinting gene expression in human nasopharyngeal carcinoma by methylation

Regulation of the H19 imprinting gene expression in human nasopharyngeal carcinoma by methylation

A Novel Ankyrin Repeat-containing Gene (Kank) Located at 9p24 Is a Growth Suppressor of Renal Cell Carcinoma

Expression of aquaporin-5 in and fluid secretion from immortalized human salivary gland ductal cells by treatment with 5-aza-2′-deoxycytidine: a possibility for improvement of xerostomia in patients with Sjögren's syndrome

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