scholarly journals Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

2002 ◽  
Vol 98 (6) ◽  
pp. 851-856 ◽  
Author(s):  
Pu Yan ◽  
Jean Benhattar ◽  
Jean-Michel Coindre ◽  
Louis Guillou
Keyword(s):  
Soft Tissue ◽  
Mrna Expression ◽  
Telomere Length ◽  
Soft Tissue Sarcomas ◽  
Telomerase Activity ◽  
Htert Mrna ◽  
Htert Mrna Expression

The Regulation of Telomere Binding Proteins on Telomerase during Differentiation of ATRA Responsive and Resistant NB4 Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3390-3390
Author(s):  
He Huang ◽  
Jie Sun ◽  
Yuan Yuan Zhu ◽  
Jian Ping Lan ◽  
Xiao Yu Lai
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Peak Level ◽  
Telomerase Activity ◽  
Expression Level ◽  
Htert Mrna ◽  
Down Regulation ◽  
Nb4 Cells ◽  
Significant Change ◽  
Htert Mrna Expression

Abstract It has been reported that the down-regulation of telomerase activity associated with maturation of APL cells is not mechanistically linked to cell maturation, and requires only a RAR, but not a RXR-dependent pathway. However, it is not clear whether and how telomeric proteins respond to the retinoid treatment. Using maturation-sensitive and resistant APL cell lines NB4, NB4-R1 and NB4-R2 cells, we analyzed a panel of telomeric proteins using western blotting analyses in addition to temporal profile of corresponding mRNA during the course of retinoid-induced differentiation. Our analyses show hTERTmRNA expression decreased rapidly during differentiation of NB4 and NB4-R1 cells, telomerase activity also declined. But in NB4-R2 cells, hTERT mRNA was initially decreased to 38.2% on day1 (P<0.05) and then increased to 80.0% on day 3 (P<0.05). Telomerase activity remained unchanged overtime (P>0.05), which may be caused by the increasing of hTERT mRNA expression during its later period of differentiation. TRF1 mRNA and protein expression have no significant change during differentiation in NB4 and NB4-R1 cells but has a small increase in NB4-R2 cells. The TRF1 mRNA expression level has no significant change during differentiation of NB4 and NB4-R1 cell line cells. However, it was increased to 235% on day 2 (P<0.05) and remains at this level until day 3 during the differentiation of NB4-R2 cells. TRF1 protein expression level also remains stable during differentiation of NB4 and NB4-R1 cells, but has a little increase in NB4-R2 cells. This indicates TRF1 has different regulation in RARα dependent or RXRα dependent pathways. Pinx1 mRNA expression decreased during the differentiation of NB4 and NB4-R1. But during the differentiation of NB4-R2, Pinx1mRNA expressions level was initially decreased to 34.3% (P<0.05) on day 1 then increased to 64.5% (P<0.05 compared to day1) on day2. The change of Pinx1 mRNA expression and hTERT mRNA expression in NB4(r=0.902, P=0.036), NB4-R1(r=1.00, P<0.001), and NB4-R2(r=0.880, P=0.049) cells are positive correlated. Pinx1 is the only telomere binding protein that can bind to hTERT directly, it might be responsible for the different regulation of telomerase activity through RARα dependent or RXRα dependent pathways. During NB4 cell differentiation, TANK1 mRNA expression decreased gradually to 31.6% (P<0.05) on day1, and remained this level until day3. In NB4-R1 cells, TANK1 mRNA expression increased initially to 197% at 12h(P<0.05), and then decreased gradually to 111% (P<0.05) on day 3. During the differentiation of NB4-R2 cells, TANK1 mRNA expression was initially increased to 204% at 12h(P<0.01), and then decreased gradually to 96.9% on day3 (P<0.01). Its protein expression initially increased and reached a peak level at day 1 and then decreased in the later period of differentiation of all three NB4 cells. Both TANK1 mRNA expression and its protein expression were down-regulated at the later period of differentiation in all three NB4 cells. It seems that TANK1 may act as a positive regulator on telomerase activity during differentiation. TANK2 mRNA expression remained no change during differentiation of three NB4 cells. As results show, Pinx1 and TANK1 may interfere in the regulation of telomerase. The decrease of TANK1 may be the cause of the down-regulation of telomerase activity. Further studies will focus on the mechanism of their regulation on telomerase.

Study on Expression of Telomerase Inhibitor Pinx1 in Leukemia Cells and Its Correlation with Telomerase Activity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4375-4375
Author(s):  
Jie Sun ◽  
He Huang ◽  
Yuanyuan Zhu ◽  
Jianping Lan ◽  
Xiaoyu Lai
Keyword(s):  
Acute Leukemia ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Telomerase Activity ◽  
Leukemia Cells ◽  
Htert Mrna ◽  
Normal Bone ◽  
Telomerase Inhibitor ◽  
Telomere Binding Protein ◽  
Htert Mrna Expression

Abstract Telomere shortens and telomerase activation was found both in malignant hematological cell line cells and leukemia samples. However, the mechanism of telomerase activation is unclear. The regulation of telomerase activity could be explained by many aspects, telomere binding protein is one of the new one. Pinx1 is an inhibitor of telomerase activity. Overexpression of Pinx1 inhibits telomerase activity, shortens telomeres, and induces crisis, whereas depletion of endogenous Pinx1 increases telomerase activity and elongates telomeres. However, how does Pinx1 act on telomerase in malignant tumor cells is not clear. In this study, we detected the expression of telomerase inhibitor Pinx1 in acute leukemia cells and during the differentiation of acute promyelocytic leukemia cells to realize its effect on telomerase activity and the probable mechanism inside. 30 acute leukemia cases were all enrolled at their first diagnose, 17 samples were of acute non-lymphocytic leukemia (ANLL) while 13 of acute lymphoblastic leukemia (ALL). Realtime quantitative PCR with fluorescence probe hybridization was used to measure expression of Pinx1 and hTERT mRNA in acute leukemia cells and during differentiation of NB4 cells induced by ATRA. NB4 cells at the initial concentration of 1×105/ml were treated with 1uM ATRA. Cells were collected at 5 time points as 0h, 12h, 24h, 48h and 72h. Pinx1 mRNA expression in acute leukemia samples(0.00312, 5.42×10−4~0.024)is significantly higher than that in normal bone marrow mononuclear cells(7.89×10−4, 0~0.00863)(P<0.01=. Both its expression in ANLL cells(0.00296, 0.00103~0.0182)( P<0.05=and ALL cells(0.00327, 5.42×10−4~0.024) (P<0.05= were higher than that in normal bone marrow mononuclear cells. The expression of Pinx1 mRNA had significant positive correlation with hTERT mRNA expression (r=0.296, P<0.05=. Pinx1 mRNA expression decreased during NB4 cell differentiation, its expression was positive correlated with hTERT mRNA expression (r=0.900, P<0.05=. Why telomerase was activated in malignant tumor cells is unclear yet. It was considered to be activated after telomere length shortened to an extent. So telomere binding proteins may play an important role in telomerase activation. Pinx1 was regarded as a negative regulator of telomerase. It was reported that Pinx1 expression was significantly reduced in many human tumor samples including liver, prostate, colon and lung carcinoma. But some studies showed Pinx1 expression has no significant change in human gastrointestinal tract carcinoma and in human hepatocellular carcinoma. We found Pinx1 expression increased in acute leukemia cells and decreased during NB4 cell differentiation, positive correlated with hTERT mRNA expression As Pinx1 is the only telomere binding protein that can bind to hTERT directly, we hypothesized that the variation of Pinx1 mRNA expression during differentiation acted as a negative feedback to hTERT for stabilization of telomerase activity. When hTERT levels increased, more Pinx1 would be bound with hTERT resulting in reduced free Pinx1 protein in cells. This in turn caused compensate increase in Pinx1 transcription. When hTERT decreased, amount of free Pinx1 protein would increase and result in decrease in Pinx1 mRNA expression. So Pinx1’s variation may be a subsequent reaction induced by that of hTERT during differentiation, though the exact mechanism needs further studies.

scholarly journals Telomerase activity and hTERT mRNA expression in glial tumors

2006 ◽  
Author(s):  
L. Boldrini ◽  
S. Pistolesi ◽  
S. Gisfredi ◽  
S. Ursino ◽  
G. Ali ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Telomerase Activity ◽  
Htert Mrna ◽  
Glial Tumors ◽  
Htert Mrna Expression

Telomerase activity and hTERT mRNA expression in body fluids

2005 ◽  
Vol 32 (3) ◽  
pp. 167-170 ◽  
Author(s):  
Yasuko Yamamoto ◽  
Eiichiro Hirakawa
Keyword(s):  
Mrna Expression ◽  
Telomerase Activity ◽  
Body Fluids ◽  
Htert Mrna ◽  
Htert Mrna Expression

scholarly journals Highly sensitive inhibition of hTERT mRNA expression and telomerase activity by DNA-signal-peptide conjugates

2005 ◽  
Vol 49 (1) ◽  
pp. 337-338
Author(s):  
Takanori Kubo ◽  
Rumiana Bakalova ◽  
Zhivko Zhelev ◽  
Hideki Ohba ◽  
Masayuki Fujii
Keyword(s):  
Mrna Expression ◽  
Signal Peptide ◽  
Telomerase Activity ◽  
Htert Mrna ◽  
Peptide Conjugates ◽  
Highly Sensitive ◽  
Htert Mrna Expression
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