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| Status |
Public on Dec 15, 2011 |
| Title |
Regulation of hTERT by BCR-ABL at multiple levels in K562 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
To investigate the mechanism of telomerase regulation in BCR-ABL positive cells due to its clinical value, we studied the catalytic component of telomerase, TERT. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at the mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells. TRAP assay also revealed that Gleevec treatment significantly reduced TA specifically in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Although Gleevec down-regulated hTERT mRNA level, the protein level of hTERT remained unchanged. Therefore, Gleevec-induced-TA decrease is not due to the alteration in telomerase subunits expression. It could be presumably due to posttranslational modification of hTERT, possibly through multiple signaling pathways. We have found that Gleevec reduced the tyrosine phosphorylation of hTERT by BCR-ABL, which is associated with the nucleoplasm localization of hTERT from nucleoli sequesters. These findings reveal unknown functions and regulations of telomerase by BCR-ABL.
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| Overall design |
Using cRNA microarray, gene expression of Gleevec-treated and non-treated K562 (BCR-ABL positive) cells were compared against Gleevec-treated and non-treated HL60 (BCR-ABL deficient) cells.
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| Contributor(s) |
Chai JH, Zhang Y, Tan WH, Chng WJ, Li B, Wang X |
| Citation(s) |
22151181 |
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| Submission date |
Jan 24, 2011 |
| Last update date |
Jan 18, 2013 |
| Contact name |
Sherry Wang |
| E-mail(s) |
[email protected]
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| Organization name |
National University of Singapore
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| Department |
Biochemistry
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| Street address |
21 Lower Kent Ridge Road
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| City |
Singapore |
| ZIP/Postal code |
119077 |
| Country |
Singapore |
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| Platforms (1) |
| GPL6104 |
Illumina humanRef-8 v2.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA136021 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26821_RAW.tar |
3.4 Mb |
(http)(custom) |
TAR |
| GSE26821_non-normalized_data.txt.gz |
2.1 Mb |
(ftp)(http) |
TXT |
| GSE26821_normalized_data_complete.txt.gz |
731.9 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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