Arsenic trioxide induced p15INK4B gene expression in myelodysplastic syndrome cell line MUTZ-1 / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanisms of arsenic trioxide (As(2)O(3)) induced demethylation.</p><p><b>METHOD</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>As(2)O(3) could activate the expression of p15 gene by demethylation or/and by inhibiting DNMT3A and DNMT3B gene.</p>