RRC ID |
41935
|
著者 |
Yamada O, Akiyama M, Kawauchi K, Adachi T, Yamada H, Kanda N, Aikawa E.
|
タイトル |
Overexpression of telomerase confers a survival advantage through suppression of TRF1 gene expression while maintaining differentiation characteristics in K562 cells.
|
ジャーナル |
Cell Transplant
|
Abstract |
Leukemic stem cells that expressed endogenous telomerase activity were induced to show overexpression of exogenous hTERT and were analyzed for biological changes in order to assess the possible influence of telomerase gene therapy on the transplantation of normal hematopoietic stem cells. Introduction of hTERT into K562, a telomerase-positive immortal cell line, resulted in a 2.5-fold elevation of telomerase activity and the lengthening of telomeres by 6 kb to 23 kb. Real-time fluorescent PCR, which could perform quantitative analysis of transcripts, revealed a 175-fold increase in hTERT expression, suggesting the posttranscriptional regulation of telomerase. Ectopic expression of hTERT in K562 cells showed a survival advantage during culture in the absence of serum. Expression of mRNA for the telomeric-repeat binding factor 1 (TRF1) and caspase-3 activity were both decreased in hTERT-transfected K562 cells. Transduced cells retained their usual phenotypic characteristics, differentiation ability, and signal transduction response to TPA. These data suggest that ectopic expression of hTERT by normal hematopoietic stem cells may confer a survival advantage without changing their innate biological characteristics.
|
巻・号 |
12(4)
|
ページ |
365-77
|
公開日 |
2003-1-1
|
DOI |
10.3727/000000003108746911
|
PMID |
12911124
|
MeSH |
Caspase 3
Caspases / metabolism
Cell Differentiation / genetics*
Cell Survival / genetics
Cellular Senescence / genetics
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic*
Humans
K562 Cells
Pyridines / pharmacology
RNA Interference / physiology
RNA, Messenger / metabolism
Signal Transduction / drug effects
Signal Transduction / genetics
Suppression, Genetic / genetics
Telomerase / genetics*
Telomerase / therapeutic use
Telomere / genetics*
Telomeric Repeat Binding Protein 1 / genetics*
Transduction, Genetic / methods
Up-Regulation / genetics
|
IF |
3.341
|
引用数 |
16
|
WOS 分野
|
TRANSPLANTATION
MEDICINE, RESEARCH & EXPERIMENTAL
CELL & TISSUE ENGINEERING
|
リソース情報 |
ヒト・動物細胞 |
K562(RCB0027) |