Bmi-1 over-expression plays a secondary role in chronic myeloid leukemia transformation
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17454639
DOI
10.1080/10428190601186002
PII: 777236060
Knihovny.cz E-resources
- MeSH
- K562 Cells MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics metabolism MeSH
- Adult MeSH
- Nuclear Proteins biosynthesis MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Small Interfering metabolism MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Polycomb Repressive Complex 1 MeSH
- Cell Proliferation MeSH
- Proto-Oncogene Proteins biosynthesis MeSH
- Gene Expression Regulation, Leukemic * MeSH
- Repressor Proteins biosynthesis MeSH
- Gene Expression Profiling MeSH
- Gene Silencing MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- BMI1 protein, human MeSH Browser
- Nuclear Proteins MeSH
- RNA, Small Interfering MeSH
- Polycomb Repressive Complex 1 MeSH
- Proto-Oncogene Proteins MeSH
- Repressor Proteins MeSH
It has been demonstrated that over-expression of Bmi-1 occurs in a variety of cancers, including several types of leukemia. This gene plays a key role in the self-renewal of stem cells. Leukemic cells lacking Bmi-1 underwent proliferation arrest and showed signs of differentiation and apoptosis. These findings led to the proposal of Bmi-1 as a potential target for therapeutic intervention in cancer. In this study, we investigated the role of Bmi-1 in chronic myeloid leukemia (CML). Using qRT-PCR, we demonstrated a significantly increased level of Bmi-1 transcript in CML cells. Using array analysis, we determined the deregulation of several genes after Bmi-1 silencing. Proapoptotic genes BAD and TRADD, and CASP8, p16-INK4, BRCA2, Notch4 and Wnt-8B were elevated. PLK1, SOD1, E2F-3, two retinoblastoma binding proteins (RBQ1 and RBBP4) and HDGF were reduced after Bmi-1 inhibition. Additionally, we tested the impact of Bmi-1 siRNA on CML cell growth; however, there was no apparent change after Bmi-1 suppression. Despite the fact that Bmi-1 deregulation occurs in CML and its expression is connected to several oncogenic processes, Bmi-1 seems to play a secondary role in CML transformation.
References provided by Crossref.org
Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBPα expression
