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  • Title: [Hypermethylation of CpG island of p16 gene and arsenic trioxide induced p16 gene demethylation in multiple myeloma].
    Author: Fu HY, Shen JZ.
    Journal: Zhonghua Nei Ke Za Zhi; 2005 Jun; 44(6):411-4. PubMed ID: 16008847.
    Abstract:
    OBJECTIVE: To investigate the role of hypermethylation of p16 gene in the pathogenesis of multiple myeloma (MM) and the effect of arsenic trioxide (As2O3) induced p16 gene demethylation. METHODS: Methylation status of p16 gene in MM and U266 cell line exposed to As2O3 were detected the nested-methylation specific PCR. The expression of p16 gene mRNA was determined with RT-PCR. The induced growth inhibition of U266 cell by growth curve and MTT and the DNA content of U266 cell were analyzed with flow cytometry after exposure to As2O3. RESULTS: Hypermethylation of CpG island of p16 gene was observed in 54.8% of the MM patients in our group. p16 gene fail to express in U266 cell line after methylation. As compared with beta-actin, the expression of p16 gene mRNA in U266 cell was increased to 0.22 +/- 0.10, 0.59 +/- 0.11, 0.68 +/- 0.09 after exposure to 0.5 micromol/L, 1.0 micromol/L and 2.0 micromol/L As2O3 for 72 h. CONCLUSIONS: These results indicate that methylation of p16 gene is essential important in the pathogenesis of MM and may provide a new diagnostic technique and drug target for the treatment of MM. As2O3 may activate the expression of p16 gene by demethylation.
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