Expression analysis of genes involved in epigenetic regulation and apoptosis in human malignant haematopoietic cell lines treated with 5-azacytidine

J BUON. 2011 Jan-Mar;16(1):116-22.

Abstract

Purpose: The aim of this study was to investigate the modulation of the expression status of 10 different genes involved in epigenetic regulation and apoptosis by the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza), as markers of response to treatment, in two different human malignant haematopoietic cell lines.

Methods: In our analysis we used the SybrGreen technology and gene-specific primers for the qRT-PCR analysis of 10 genes, in cDNA of PC-MDS and K562 cell lines, treated by 1 micromole of 5-Aza for 24h.

Results: DNMT1 and DNMT3A showed statistically significant decrease of expression in 5-Aza-treated PC-MDS cells, whereas DNMT3B showed significantly decreased expression in 5-Aza-treated K562 cells. The members of the Bcl- 2 family of apoptosis-regulating genes Bcl-2 and Bax showed statistically significant differences in expression, in comparison with non-treated PC-MDS cells. Our most interesting result was the significant upregulation (re-expression) of p15, in 5-Aza-treated PC-MDS cells.

Conclusion: The re-expression of p15 in PC-MDS cell line evaluated by qRT-PCR makes this novel cell line a suitable model for the studies of pharmacologic demethylation as a plausible mechanism resulting in hematologic response in myelodysplastic syndrome (MDS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis*
  • Azacitidine / pharmacology*
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methyltransferase 3A
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • K562 Cells
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / pathology
  • Oxidative Stress
  • RNA, Messenger / analysis

Substances

  • Antimetabolites, Antineoplastic
  • DNMT3A protein, human
  • RNA, Messenger
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNMT1 protein, human
  • Azacitidine