Expression analysis of PCNA gene in chronic myelogenous leukemia--combined application of siRNA silencing and expression arrays
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17070905
DOI
10.1016/j.leukres.2006.10.004
PII: S0145-2126(06)00386-9
Knihovny.cz E-resources
- MeSH
- Apoptosis MeSH
- Fusion Proteins, bcr-abl metabolism MeSH
- Benzamides MeSH
- Drug Resistance, Neoplasm MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy genetics MeSH
- Imatinib Mesylate MeSH
- Humans MeSH
- RNA, Small Interfering pharmacology MeSH
- RNA, Messenger genetics metabolism MeSH
- Biomarkers, Tumor genetics MeSH
- Tumor Cells, Cultured MeSH
- Piperazines therapeutic use MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Cell Proliferation MeSH
- Proliferating Cell Nuclear Antigen genetics MeSH
- Pyrimidines therapeutic use MeSH
- Gene Expression Regulation, Leukemic * MeSH
- RNA, Neoplasm genetics metabolism MeSH
- Oligonucleotide Array Sequence Analysis * MeSH
- Gene Expression Profiling * MeSH
- Gene Silencing * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fusion Proteins, bcr-abl MeSH
- Benzamides MeSH
- Imatinib Mesylate MeSH
- RNA, Small Interfering MeSH
- RNA, Messenger MeSH
- Biomarkers, Tumor MeSH
- Piperazines MeSH
- Proliferating Cell Nuclear Antigen MeSH
- Pyrimidines MeSH
- RNA, Neoplasm MeSH
Imatinib metylase is the first choice treatment for BCR/ABL positive chronic myelogenous leukemia (CML). However, as some CML patients develop resistance to imatinib therapy, there is a significant interest in development of alternative treatment strategies, such as identifying targets other than BCR/ABL that may participate in CML. Previously, we demonstrated strong PCNA up-regulation in CML patients. To further study its role in CML pathogenesis, we performed silencing of PCNA expression followed by array experiments. PCNA inhibition led to down-regulation of CDK1, CDK4, PLK1, ERK3, JNK1, STAT5, and several inhibitors of apoptosis (DAXX, Mdm2, survivin). The following genes were up-regulated: CDK inhibitors p21 and p19-INK4D, pro-apoptotic FAST kinase, fibronectin, etc. However, as PCNA affects cell growth in naturally proliferating cells as well as in cancerous cells, it seems to act a secondary role relating to proliferation activity of leukemic cells.
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