論文 - 詳細
| RRC ID | 77019 |
|---|---|
| 著者 | Weeks RJ, Ludgate JL, LeMée G, Morison IM. |
| タイトル | TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells. |
| ジャーナル | PLoS One |
| Abstract |
BACKGROUND:Childhood acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity. METHODS:Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5'-aza-2'-deoxycytidine (decitabine) exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays. RESULTS:In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity. CONCLUSIONS:These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL. |
| 巻・号 | 11(3) |
| ページ | e0151341 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pone.0151341 |
| PII | PONE-D-15-28544 |
| PMID | 26985820 |
| PMC | PMC4795691 |
| MeSH | Cell Cycle / genetics Cell Line, Tumor Cell Proliferation / genetics* Cytoskeletal Proteins / genetics* Cytoskeletal Proteins / metabolism DNA Methylation* Gene Expression Regulation, Neoplastic Humans LIM Domain Proteins / genetics* LIM Domain Proteins / metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics* Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology Promoter Regions, Genetic* RNA-Binding Proteins Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | NALM-6(RCB1933) |