Epigenetic Inactivation of <b>
                     <i>TMS1/ASC</i>
                  </b> in Ovarian Cancer

Terasawa, Katsuhiko; Sagae, Satoru; Toyota, Minoru; Tsukada, Kuniko; Ogi, Kazuhiro; Satoh, Ayumi; Mitsuya, Hiroaki; Imai, Kohzoh; Tokino, Takashi; Kudo, Ryuichi

doi:10.1158/1078-0432.ccr-0932-03

Cited by 81 publications

(25 citation statements)

References 29 publications

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“…We also sought to analyse the methylation in RCC of other well-known tumor-associated genes that are frequently methylated in other cancers (Herman et al, 1996(Herman et al, , 1998Katzenellenbogen et al, 1999;Toyota et al, 1999aToyota et al, , c, 2003Esteller et al, 2000;Baylin et al, 2001;Sato et al, 2001;Ogi et al, 2002;Kikuchi et al, 2002;Herman and Baylin, 2003;Satoh et al, 2003;Okami et al, 2004;Terasawa et al, 2004) to clarify whether the frequent inactivation of HOXB13 in primary RCC is significant. We could not detect the methylation of p14ARF, p15INK4B, p16INK4A, BNIP3, hMLH1, DCC, and MINT2, and only low methylation frequencies (o18%) in CHFR, CACNA1G, TMS1, DAPK, COX-2, and MINT1 were detected, suggesting that these genes are not the main targets for methylation in RCC.…”

Section: Discussionmentioning

confidence: 99%

“…The restriction enzyme used for HOXB13 was BstUI (New England Biolabs). The primer sequences, PCR parameters, and the restriction enzymes used for the COBRA of other genes (p14ARF, p15INK4B, p16INK4A, CHFR, CACNA1G, TMS1, BNIP3, COX-2, hMLH1, DAPK, DCC, MINT1, and MINT2) have been described previously (Kikuchi et al, 2002;Ogi et al, 2002;Satoh et al, 2003;Terasawa et al, 2004). The resultant DNA fragments were electrophoresed in 2.5% agarose gels and stained with ethidium bromide.…”

Section: Cobramentioning

confidence: 99%

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Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma

Okuda¹,

Toyota

Ishida

et al. 2005

Oncogene

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Epigenetic alterations like DNA methylation and the resulting inactivation of cancer-related genes often contribute to the development of various cancers. To identify the genes that are silenced by aberrant methylation in renal cell carcinoma (RCC), we subjected two RCC lines to methylated CpG island amplification/representational difference analysis. This identified 27 CpG islands. Combined bisulfite restriction analysis of these CpG islands in primary RCC cases revealed that four were methylated in a tumor-specific manner. One of these was identified as the human homeo-box gene B13 (HOXB13) gene, but the remaining three CpG islands were not associated with known genes. The methylation frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%, respectively. The methylation status of HOXB13 correlated with the loss of its expression both in RCC lines and primary tumors, and methyltransferase inhibitor treatment induced the recovery of its expression. Exogenous expression of HOXB13 in RCC cells that lacked endogenous HOXB13 expression suppressed colony formation and induced apoptotic features. Furthermore, HOXB13 methylation correlated positively with tumor grade and microvessel invasion. These results suggest that HOXB13 is a novel candidate tumor suppressor gene in RCC and that its inactivation may play an important role in both RCC tumorigenesis and progression.

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Section: Discussionmentioning

confidence: 99%

Section: Cobramentioning

confidence: 99%

Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma

Okuda¹,

Toyota

Ishida

et al. 2005

Oncogene

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“…Two independent bisulfite modifications were performed, and five independent MSPs and real-time MSPs were performed. Representative bands of MSP are shown in the figures 52 .…”

Section: Methodsmentioning

confidence: 99%

Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes

Hara

Wakino

Šimić

et al. 2013

Nat Med

411

361

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The protective role of Sirt1 in renal damage was investigated. Sirt1 in proximal tubules (PT) was downregulated before albuminuria occurred in streptozotocin-induced or obese-type (db/db) diabetic mice. PT-specific Sirt1 transgenic (TG) and knockout (KO) mice showed prevention and aggravation of the glomerular changes occurring in diabetes, respectively, and non-diabetic KO mice exhibited albuminuria, suggesting that Sirt1 in PT affects glomerular function. Downregulation of Sirt1 and upregulation of the tight junction protein Claudin-1 by Sirt1-mediated epigenetic regulation in podocytes contributed to albuminuria. These phenomena were not observed in 5/6 nephrectomized mice. We also demonstrated retrograde interplay from PT to glomeruli using nicotinamide mononucleotide (NMN) from conditioned medium, measurement of the auto-fluorescence of photoactivatable NMN, and injection of fluorescence-labeled NMN. In human subjects with diabetes, Sirt1 and Claudin-1 levels were correlated with proteinuria level. Sirt1 in PT protects against albuminuria in diabetes through maintaining NMN concentrations around glomeruli and controlling podocyte function.

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“…Variation in the P2 promoter of HNF4A , presumably leading to a decrease in HNF4A expression, has been associated with an increased risk of developing Type 2 diabetes (Weedon et al 2004), whilst bi-allelic inactivation of HNF1A and HNF1B has been shown to cause a number of types of cancer (Bluteau et al 2002; Terasawa et al 2004; Rebouissou et al 2005). As it has for monogenic diabetes, continued research in the area of RNA processing and mRNA surveillance may provide fascinating insights into the pathogenesis behind these diseases as well as other diabetes-related phenotypes such as renal disease and hyperinsulinaemic hypoglycaemia.…”

Section: Discussionmentioning

confidence: 99%

RNA Processing and mRNA Surveillance in Monogenic Diabetes

Locke

Harries

2008

Gene�Regul Syst Bio

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In the eukaryotic cell a number of molecular mechanisms exist to regulate the nature and quantity of transcripts intended for translation. For monogenic diabetes an understanding of these processes is aiding scientists and clinicians in studying and managing this disease. Knowledge of RNA processing and mRNA surveillance pathways is helping to explain disease mechanisms, form genotype-phenotype relationships, and identifying new regions within genes to screen for mutations. Furthermore, recent insights into the regulatory role of micro RNAs (miRNAs) and RNA editing in the pancreas suggests that these mechanisms may also be important in the progression to the diabetic state.

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Epigenetic Inactivation of TMS1/ASC in Ovarian Cancer

Cited by 81 publications

References 29 publications

Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma

Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma

Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes

RNA Processing and mRNA Surveillance in Monogenic Diabetes

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