Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells

Wong, Nicholas C.; Novakovic, Boris; Weinrich, B; Dewi, C; Andronikos, Roberta; Sibson, Mandy; Macrae, Finlay; Morley, Ruth; Pertile, Mark D.; Craig, Jeffrey M; Saffery, Richard

doi:10.1016/j.canlet.2008.03.033

Cited by 68 publications

(50 citation statements)

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“…Table 1 presents an annotated list of the probes and Figure 5 shows their methylation levels in cytotrophoblasts and fibroblasts for the genes represented by multiple probes. Two genes, APC 19,20 and RASSF1, 21 have been previously reported to exhibit unique methylation patterns in placentas and in cancer. Others not previously reported (TP73, RASSF5, DAB2IP, PRKCDBP, MORF4L1) are also shown by our data to have probes in the promoter region that are more methylated in (Fig.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…26,27 Some of these same promoter regions have also been reported to be methylated in placenta. [19][20][21]28 On the other hand, most normal tissues exhibit low methylation in these genomic regions, suggesting some molecular methylation signatures of tumor suppressor genes are shared by tumors and placenta. If this epigenetic signature is driven by the placental cell type with invasive behavior, it would be expected that methylation of tumor suppressor genes in cytotrophoblasts should be higher than in fibroblasts.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

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Cell specific patterns of methylation in the human placenta

Grigoriu¹,

Ferreira²,

Choufani³

et al. 2011

Epigenetics

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Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Cell specific patterns of methylation in the human placenta

Grigoriu¹,

Ferreira²,

Choufani³

et al. 2011

Epigenetics

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“…Tissue sections from other species were washed briefly in saline before processing by maceration with a scalpel blade prior to immediate DNA isolation. CVS samples were collected and processed as previously described (37).…”

Section: Methodsmentioning

confidence: 99%

Placenta-specific Methylation of the Vitamin D 24-Hydroxylase Gene

Novakovic

Sibson

et al. 2009

Journal of Biological Chemistry

220

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Plasma concentrations of biologically active vitamin D (1,25-(OH)2D) are tightly controlled via feedback regulation of renal 1␣-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH) 2 D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitamin D deregulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface.In eutherian mammals, proper fetal growth and development are dependent on the formation and function of the placenta. In combination with the maternal decidua, cells of the placenta (primarily trophoblasts) regulate the exchange of nutrients, growth factors, oxygen, and waste between maternal and fetal circulations. The placenta also protects the developing pregnancy from the maternal immune system (1).Although mammalian placentas share a basic common function in modulating exchange at the fetomaternal interface, it is clear that the human placenta is unique in structure and function (2). Animal models may therefore be of limited value in fully dissecting processes underlying certain aspects of human pathologies, such as pre-eclampsia and gestational trophoblastic disease (3). An examination of human placentation is therefore critical in understanding its unique function and potential role in disease.The biologically active form of vitamin D (1,25-(OH) 2 D) 4 is a potent secosteroid hormone. Its wide ranging actions include regulating calcium and phosphorus homeostasis, immune system modulation, cellular differentiation, and apoptosis (4 -6). It also has potent antiproliferative effects (7-9). Vitamin D deficiency has been linked to several adverse pregnancy outco...

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“…The human APC gene promoter region hypermethylation is present in different types of cancers and in some pre-cancerous tissues (Hiltunen et al, 1997;Jin et al, 2001;Wong et al, 2008). In the present study, APC methylation was higher in ovarian malignant tissues than in NAT.…”

Section: 2719 Methylation Of Sfrps Genes In Ovarian Cancer Infected mentioning

confidence: 46%