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.
Original language | English |
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Pages (from-to) | 56-62 |
Number of pages | 7 |
Journal | Cancer Letters |
Volume | 268 |
Issue number | 1 |
DOIs | |
Publication status | Published - 8 Sep 2008 |
Externally published | Yes |
Keywords
- Adenamatous polyposis coli
- Epigenetics
- Methylation
- Placenta
- Tumour suppressor