Trichostatin A suppresses transformation by the v-myb oncogene in BM2 cells.
BM2 cells are chicken monoblasts transformed by the v-myb oncogene of avian myeloblastosis virus. The constitutively high v-myb expression interferes with the terminal differentiation of BM2 cells, but these cells can be induced to differentiate into macrophage-like cells by phorbol esters. Histone acetylation plays an important role in regulation of transcription and is particularly relevant to the regulation and pathology of hematopoiesis. In the present study, we examined the contribution of elevated histone acetylation to the differentiation of BM2 cells. Inhibition of the activity of endogenous histone deacetylases by trichostatin A (TSA) resulted in histone hyperacetylation causing cell cycle arrest and differentiation of BM2 cells into macrophage polykaryons. TSA did not affect the level of v-Myb protein in BM2 cells, but it downregulated its transcription activation capability. This suggests that chromatin remodeling can be significantly engaged in regulation of proliferation and differentiation of leukemic cells.
Nemajerová
Alice
A
Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Smarda
Jan
J
Jurdic
Pierre
P
Kubala
Lukás
L
Soucek
Karel
K
Smardová
Jana
J
D000107:Acetylation; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002645:Chickens; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D020570:Genes, myb / Q000187:drug effects / Q000502:physiology*; D006655:Histone Deacetylases / Q000187:drug effects; D006657:Histones / Q000378:metabolism / Q000502:physiology; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology
D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D006655:Histone Deacetylases