Nuclear topography and expression of the BCR/ABL fusion gene and its protein level influenced by cell differentiation and RNA interference
Language English Country Great Britain, England Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15978941
DOI
10.1016/j.leukres.2005.01.011
PII: S0145-2126(05)00055-X
Knihovny.cz E-resources
- MeSH
- Antigens, Surface drug effects genetics MeSH
- Apoptosis drug effects physiology MeSH
- Fusion Proteins, bcr-abl genetics MeSH
- Cell Differentiation drug effects physiology MeSH
- Cell Nucleus drug effects genetics metabolism MeSH
- K562 Cells MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics metabolism pathology MeSH
- Down-Regulation MeSH
- HL-60 Cells MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Cell Line, Tumor MeSH
- Gene Expression Regulation, Leukemic * MeSH
- RNA Interference physiology MeSH
- Tetradecanoylphorbol Acetate analogs & derivatives pharmacology MeSH
- Blotting, Western MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Antigens, Surface MeSH
- Fusion Proteins, bcr-abl MeSH
- phorbolol myristate acetate MeSH Browser
- Tetradecanoylphorbol Acetate MeSH
Nuclear topography, expression of the BCR/ABL fusion gene and its protein level/cellular pattern were studied in CML cell line K562 stimulated to differentiation, apoptosis and influenced by ABL-RNA interference (ABL-RNAi). Phorbol ester-induced maturation of K562 cells was accompanied by repositioning of down-regulated BCR/ABL genes closer to the nuclear membrane. This nuclear rearrangement could be connected with differentiation-related heterochromatinization of the amplified BCR-ABL locus, as demonstrated by increased histone H3(K9) dimethylation and decreased H3(K9) acetylation of B3A2 breakpoint. Topography of BCR/ABL in differentiated K562 cells was compared with other leukemic cell types: PMA-maturation of HL60 cells did not influence the nuclear positioning of individual BCR and ABL genes. Moreover, BCR and ABL genes in non-stimulated HL60 as well as in the bone marrow cells of CML patients, i.e. also BCR/ABL fusion genes, were positioned more interiorly in comparison with BCR/ABL multiple loci of K562 cells. Decreased expression of BCR/ABL gene was also found after cell stimulation by selectively pro-apoptotic agent etoposide and by ABL-RNAi leading to apoptosis. In order to compare the efficiency of selected experimental strategies, levels of Bcr/Abl and c-Abl proteins were determined and in all cases tested were reduced. In K562 cells the Bcr/Abl and c-Abl proteins were distributed homogeneously in both the cell nucleus and cytoplasm, while differentiation of K562 cells was characterized by a distinct pattern of Bcr/Abl and c-Abl proteins that were focally distributed rather in the cytoplasm while apoptotic population was completely absent of Bcr/Abl and c-Abl signals.
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