Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells |
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Authors: | Wong N C Novakovic B Weinrich B Dewi C Andronikos R Sibson M Macrae F Morley R Pertile M D Craig J M Saffery R |
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Affiliation: | Epigenetics Research, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria 3052, Australia; Department of Paediatrics, University of Melbourne, Australia. |
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Abstract: | Methylation of the human APC gene promoter is associated with several different types of cancers and has also been documented in some pre-cancerous tissues. We have examined the methylation of APC gene promoters in human placenta and choriocarcinoma cells. This revealed a general hypomethylation of the APC-1b promoter and a pattern with monoallelic methylation of the APC-1a promoter in full term placental tissue. However, there was no evidence of a parent-of-origin effect, suggesting random post zygotic origin of methylation. Increased methylation of this promoter was observed in all choriocarcinoma-derived trophoblast cell lines, suggesting a trophoblastic origin of placental APC methylation and implicating APC hypermethylation in the development of this group of gestational tumours. Our demonstration of placental methylation of the APC-1a promoter represents the first observation of monoallelic methylation of this gene in early development, and provides further support for a role of canonical Wnt signalling in placental trophoblast invasiveness. This also implicates tumour suppressor gene silencing as an integral part of normal human placental development. |
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Keywords: | Epigenetics Tumour suppressor Adenamatous polyposis coli Placenta Methylation |
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