1. Hypermethylation of RASSF1A in human and rhesus placentas.
- Author
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Chiu RW, Chim SS, Wong IH, Wong CS, Lee WS, To KF, Tong JH, Yuen RK, Shum AS, Chan JK, Chan LY, Yuen JW, Tong YK, Weier JF, Ferlatte C, Leung TN, Lau TK, Lo KW, and Lo YM
- Subjects
- Amino Acid Sequence, Animals, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Cell Line, Tumor, DNA Primers, Female, Gene Expression, Genes, Tumor Suppressor, Humans, Immunohistochemistry, Lasers, Macaca mulatta, Mice, Microdissection, Molecular Sequence Data, Pregnancy, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, DNA Methylation, Epigenesis, Genetic, Placenta physiology, Tumor Suppressor Proteins genetics
- Abstract
The pseudomalignant nature of the placenta prompted us to search for tumor suppressor gene hypermethylation, a phenomenon widely reported in cancer, in the human placenta. Nine tumor suppressor genes were studied. Hypermethylation of the Ras association domain family 1 A (RASSF1A) gene was found in human placentas from all three trimesters of pregnancy but was absent in other fetal tissues. Hypermethylation of Rassf1 was similarly observed in placentas from the rhesus monkey but not the mouse. An inverse relationship between RASSF1A promoter methylation and gene expression was demonstrated by bisulfite sequencing of microdissected placental cells and immunohistochemical staining of placental tissue sections using an anti-RASSF1A antibody. Treatment of choriocarcinoma cell lines, JAR and JEG3, by 5-aza-2'-deoxycytidine and trichostatin A led to reduction in RASSF1A methylation but increased expression. These observations extend the analogy between the primate placenta and malignant tumors to the epigenetic level.
- Published
- 2007
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