Gene inactivation of the cyclin-dependent kinase inhibitors p16INK4a, p15INK4b and p21WAF is frequently mediated by promoter gene methylation, whereas histone deacetylases (HDACs) control gene expression through their ability to deacetylate proteins. The effect of suberohydroxamic acid (SBHA) and 5-Aza-2'-deoxycytidine (Decitabine) (DAC) treatments on the transcription of CDKN2A, CDKN2B and CDKN1A genes, and their effects on molecular biological behavior were examined in two myeloma cell lines, RPMI8226 and U266, which differ in p53-functionality and IL-6 expression. In both tested myeloma cell lines, a non-methylated state of the CDKN2B gene promoter region was detected with normal gene expression, and the same level of p15INK4b protein was detected by immunocytochemical staining. Furthermore, in myeloma cells treated with SBHA and DAC alone, the expression of both p15INK4b and p21WAF was significantly upregulated in RPMI8226 cells (p53-functional, without IL-6 expression), whereas in the U266 cell line (p53 deleted, expressing IL-6) only p21WAF expression was significantly increased. Moreover, the analysis revealed that treatment with DAC induced DNMT3B enhancement in U266 cells. In conclusion, in myeloma cells with IL-6 expression, significantly increased DNMT3B expression indicated the tumorigenic consequences of 5-Aza-2'deoxycytidine treatment, which requires careful use in diseases involving epigenetic dysregulation, such as multiple myeloma (MM).

• MeSH
• decitabin * farmakologie   MeSH
• DNA-(cytosin-5-)methyltransferasa * genetika   metabolismus   MeSH
• epigeneze genetická * MeSH
• inhibitor p15 cyklin-dependentní kinasy genetika   metabolismus   MeSH
• inhibitor p16 cyklin-dependentní kinasy genetika   metabolismus   MeSH
• interleukin-6 genetika   metabolismus   MeSH
• lidé MeSH
• metylace DNA MeSH
• mnohočetný myelom * genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• umlčování genů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH