Telomerase activity is down regulated via decreases in hTERT mRNA but not TEP1 mRNA or hTERC during the differentiation of leukemic cells.
BACKGROUND
Recent studies have determined several telomerase-associated molecules, but the precise mechanisms regulating telomerase activity by those molecules has not been fully understood.


METHODS
The telomerase activity was determined by TRAP assay. Using TaqMan RT-PCR, the quantitative and kinetic values of mRNA expression of the three telomerase-associated molecules were examined in HL60 cells differentiated with tumor necrosis factor mutant and all-transretinoic acid.


RESULTS
The levels of telomerase activity in leukemic cell lines, leukemic cells from patients, and normal peripheral blood cells were distributed over a very wide range. Human telomerase catalytic subunit (hTERT) mRNA expression declined to nearly undetectable levels more rapidly than the inhibition of telomerase activity after treatment with these reagents in HL60 cells. Telomerase-associated protein (TEP1) mRNA increased approximately 6-fold over its level in untreated cells. The levels of human telomerase RNA component (hTERC) also increased approximately 2.7-fold at 5 days after treatment.


CONCLUSIONS
These results suggest that telomerase activity is down-regulated mainly via decreases in hTERT, but not TEP1 and hTERC expression during the differentiation of leukemic cells.
Koyanagi
Y
Y
Department of Laboratory Diagnosis, Sapporo Medical University, School of Medicine, Japan.
Kobayashi
D
D
Yajima
T
T
Asanuma
K
K
Kimura
T
T
Sato
T
T
Kida
T
T
Yagihashi
A
A
Kameshima
H
H
Watanabe
N
N
D000293:Adolescent; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D020134:Catalytic Domain; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D015448:Leukemia, B-Cell; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D015458:Leukemia, T-Cell; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; C104342:TEP1 protein, human; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase