1. Epigenetics of multiple myeloma after treatment with cytostatics and gamma radiation
- Author
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Krejčí, Jana, Harničarová, Andrea, Štreitová, Denisa, Hájek, Roman, Pour, Luděk, Kozubek, Stanislav, and Bártová, Eva
- Subjects
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MULTIPLE myeloma treatment , *EPIGENESIS , *HISTONES , *ACETYLATION , *CANCER cells , *PROMOTERS (Genetics) , *CANCER chemotherapy ,THERAPEUTIC use of gamma rays - Abstract
Abstract: Genetic and epigenetic changes in multiple myeloma (MM) correlate with the stage of the disease. Therefore, we investigated how cytostatics and gamma radiation influence MM-associated histone modifications. ChIP-PCR and ChIP-on-chip technologies were used to quantify H3K9 acetylation and H3K9 dimethylation at select loci in MM patients, lymphoblastoid ARH-77, and myeloma MOLP-8 cells. Genome-wide analysis revealed that the cytostatic, melphalan, increased H3K9 acetylation at multiple gene promoters in ARH-77 cells. Melphalan and gamma radiation also influenced histone modification of prognostically important c-myc and CCND1 genes in ARH-77 and MOLP-8 cells. Moreover, H3K9 acetylation at c-myc and CCND1 promoters was increased in individual MM patients after melphalan treatment. Western blotting revealed that these effects were accompanied by changes in c-MYC and cyclin D1 protein levels. Taken together, we showed that cytostatics significantly alter histone modification of tumor-related genes which is indispensable for understanding cancer therapies. [Copyright &y& Elsevier]
- Published
- 2009
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