[Hypermethylation of CpG island of p16 gene and arsenic trioxide induced p16 gene demethylation in multiple myeloma].
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.
Fu
Hai-ying
HY
Fujian Institute of Hematology, Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Shen
Jian-zhen
JZ
D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics
D000970:Antineoplastic Agents; D001152:Arsenicals; D019941:Cyclin-Dependent Kinase Inhibitor p16; D010087:Oxides; D012333:RNA, Messenger; D000077237:Arsenic Trioxide