[Arsenic trioxide induced p15INK4B gene expression in myelodysplastic syndrome cell line MUTZ-1].
OBJECTIVE
To investigate the mechanisms of arsenic trioxide (As(2)O(3)) induced demethylation.


METHODS
Methylation of p15INK4B gene in MUTZ-1 cell was detected by PCR using a methylation specific primer (MSP), the expression of P15, DNA methyltransferase (DNMT) 1, DNMT3A and DNMT3B gene by RT-PCR, the As(2)O(3) induced growth inhibition of MUTZ-1 cell by MTT method.


RESULTS
P15 gene failed to express in MUTZ-1 cells after methylation. The expression was recovered after the cells exposed to As(2)O(3). As(2)O(3) could significantly down-regulate DNMT3A and DNMT3B but not DNMT1 gene on mRNA level in a dose dependent manner.


CONCLUSIONS
As(2)O(3) could activate the expression of p15 gene by demethylation or/and by inhibiting DNMT3A and DNMT3B gene.
Tong
Hongyan
H
The First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310003, China.
Lin
Maofang
M
D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D000090205:DNA Methyltransferase 3A; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001152:Arsenicals; D050762:Cyclin-Dependent Kinase Inhibitor p15; C000717967:DNMT3A protein, human; D010087:Oxides; D012333:RNA, Messenger; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C000619380:DNMT1 protein, human; D000077237:Arsenic Trioxide