scholarly journals Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity

2002 ◽  
Vol 101 (4) ◽  
pp. 335-341 ◽  
Author(s):  
Isabelle Guilleret ◽  
Pu Yan ◽  
Fabienne Grange ◽  
Richard Braunschweig ◽  
Fred T. Bosman ◽  
...  
Keyword(s):  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Htert Gene ◽  
Human Telomerase

scholarly journals Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT

2016 ◽  
Vol 62 (5) ◽  
pp. 544-554 ◽  
Author(s):  
D.D. Zhdanov ◽  
D.A. Vasina ◽  
E.V. Orlova ◽  
V.S. Orlova ◽  
M.V. Pokrovskaya ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Over Expression ◽  
Htert Gene ◽  
Template Strand ◽  
Non Coding Rna ◽  
Dna Strand ◽  
Human Telomerase ◽  
Long Non Coding Rna

Human telomerase catalytic subunit hTERT is subjected to alternative splicing results in loss of its function and leads to decrease of telomerase activity. However, very little is known about the mechanism of hTERT pre-mRNA alternative splicing. Apoptotic endonuclease EndoG is known to participate this process. The aim of this study was to determine the role of EndoG in regulation of hTERT alternative splicing. Increased expression of b-deletion splice variant was determined during EndoG over-expression in CaCo-2 cell line, after EndoG treatment of cell cytoplasm and nuclei and after nuclei incubation with EndoG digested cell RNA. hTERT alternative splicing was induced by 47-mer RNA oligonucleotide in naked nuclei and in cells after transfection. Identified long non-coding RNA, that is the precursor of 47-mer RNA oligonucleotide. Its size is 1754 nucleotides. Based on the results the following mechanism was proposed. hTERT pre-mRNA is transcribed from coding DNA strand while long non-coding RNA is transcribed from template strand of hTERT gene. EndoG digests long non-coding RNA and produces 47-mer RNA oligonucleotide complementary to hTERT pre-mRNA exon 8 and intron 8 junction place. Interaction of 47-mer RNA oligonucleotide and hTERT pre-mRNA causes alternative splicing.

scholarly journals Events in the immortalizing process of primary human mammary epithelial cells by the catalytic subunit of human telomerase

2002 ◽  
Vol 365 (3) ◽  
pp. 765-772 ◽  
Author(s):  
Hyunggee KIM ◽  
James FARRIS ◽  
Shelly A. CHRISTMAN ◽  
Byung-Whi KONG ◽  
Linda K. FOSTER ◽  
...  
Keyword(s):  
Single Copy ◽  
Telomerase Activity ◽  
Genetic Alterations ◽  
Mammary Epithelial ◽  
Catalytic Subunit ◽  
Early Passage ◽  
Htert Gene ◽  
Human Mammary Epithelial ◽  
Human Telomerase

The in vitro immortalization of primary human mammary epithelial (HME) cells solely by the exogenous introduction of the catalytic subunit of human telomerase (hTERT) has been achieved. Early passage hTERT-transfected HME (T-HME) cells continuously decreased the length and density of telomeres even in the presence of telomerase activity, with a significant number of cells staining positive for senescence-associated β-galactosidase (SA-β-gal). Subsequently, with the increase in cell passages, the copy number of the exogenously transfected hTERT gene and the percentage of SA-β-gal positive cells were found to decrease. Eventually, a single copy of the exogenous hTERT gene was observed in the relatively later passage T-HME cells in which telomere length was elongated and stabilized without obvious activation of endogenous hTERT and c-Myc expression. In T-HME cells, the expression of two p53 regulated genes p21WAF and HDM2 increased (as in primary senescent HME cells), and was found to be further elevated as the function of p53 was activated by treatment with DNA-damaging agents. p16INK4a was shown to be significantly higher in the primary senescent HME and the early passage T-HME cells when compared with the primary presenescent HME cells, with a dramatic repression of p16INK4a observed in the later passage T-HME cells. In addition, the expression of E2F1 and its transcription factor activity were found to be significantly higher in the later passage T-HME cells when compared with the earlier passage T-HME cells. Together, our results indicate that in vitro immortalization in HME cells may require the activation of the function of telomerase and other genetic alterations such as the spontaneous loss of p16INK4a expression.

scholarly journals Induction of apoptotic endonuclease EndoG with DNA-damaging agents initiates alternative splicing of telomerase catalytic subunit hTERT and inhibition of telomerase activity hTERT in human CD4+ and CD8+ T-lymphocytes

2017 ◽  
Vol 63 (4) ◽  
pp. 296-305 ◽  
Author(s):  
D.D. Zhdanov ◽  
D.A. Vasina ◽  
V.S. Orlova ◽  
E.V. Orlova ◽  
D.V. Grishin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
T Lymphocytes ◽  
Splice Variants ◽  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Human Telomerase Reverse Transcriptase ◽  
Dna Damages ◽  
Dna Damaging Agents ◽  
Cd8 T Lymphocytes ◽  
Human Telomerase

Activity of telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase) can be regulated by alternative splicing of its mRNA. At present time exact mechanism of hTERT splicing is not fully understood. Apoptotic endonuclease EndoG is known to participate this process. EndoG expression is induced by DNA damages. The aim of this work was to investigate the ability of DNA-damaging agents with different mechanism of action to induce EndoG expression and inhibit telomerase activity due to the activation of hTERT alternative splicing in normal activated human CD4+ and CD8+ T-lymphocytes. All investigated DNA-damaging agents were able to induce EndoG expression. Cisplatin, a therapeutic compound, producing DNA cross-links induced the highest level of DNA damages and EndoG expression. Incubation of CD4+ and CD8+ T-cells with cisplatin caused the changes in proportion of hTERT splice variants and inhibition of telomerase activity.

Telomerase activity and expression of human telomerase catalytic subunit gene in esophageal tissues

2002 ◽  
Vol 37 (6) ◽  
pp. 418-427 ◽  
Author(s):  
Tatsuro Tominaga ◽  
Hiromasa Kashimura ◽  
Kaori Suzuki ◽  
Akira Nakahara ◽  
Naomi Tanaka ◽  
...  
Keyword(s):  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Subunit Gene ◽  
Human Telomerase

scholarly journals An Alternate Splicing Variant of the Human Telomerase Catalytic Subunit Inhibits Telomerase Activity

Neoplasia ◽  
2000 ◽  
Vol 2 (5) ◽  
pp. 433-440 ◽  
Author(s):  
Xiaoming Yi ◽  
Dennis M. White ◽  
Dara L. Aisner ◽  
Joseph A. Baur ◽  
Woodring E. Wright ◽  
...  
Keyword(s):  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Alternate Splicing ◽  
Splicing Variant ◽  
Human Telomerase

scholarly journals The Expression of Human Telomerase Reverse Transcriptase in Adult Acute Myeloid Leukemia and Its Correlation With Various Clinico-Pathological Parameters

2019 ◽  
Vol 11 (4) ◽  
pp. 25
Author(s):  
Farah AlJobori ◽  
Abdulkareem Mohammad Jaafar
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Htert Gene ◽  
Human Telomerase ◽  
Hematological Remission ◽  
Acute Myeloid

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal expansion of myeloid progenitors (blasts) in the bone marrow and peripheral blood, AML accounts for 80% of acute leukemia in adults, its incidence increase with age. AML can be a fatal disease so research to predict prognosis is important. Telomerase (TA) is an enzyme that stabilizes the telomere length and makes the cell immortal. It is present in some of the normal cells, fetal cells, adult germ cells, and presents in 85% of tumors in humans, it has been shown that TA can be used as a prognostic marker in some solid and hematological neoplasms. Telomere length is a factor that predicts telomere function. AIM: We test the quantitative amount of human telomerase reverse transcriptase (hTERT) gene expression in AML (diagnosed according to FAB) adult and its correlation with various clinic-pathological parameters. PATIENTS & METHODS: We used the TRAP assay to assess the hTERT gene expression in mononuclear blood cells from 40 newly diagnosed AML patients, 25 AML patients after completing their course of treatment, and 15 control health subjects. RESULTS: The mean value of hTERT in AML and control groups were [1.59 ± 1.27 anm and 0.035 ± 0.046 anm respectively], and this difference was significantly higher in patients than in control group (p = 0.0001). The telomerase activity was positive in 27 (67.5%) AML patients, while 13 (32.5%) AML patients were negative for telomerase activity. Twenty-five patients after induction chemotherapy were followed up by bone marrow and peripheral blood examination to determine the patient’s response to therapy. Complete hematological remission was achieved in 12 (48.0%) patients and incomplete hematological remission in 13 (52.0%) patients (14%). The hTERT level was significantly higher in patients before induction chemotherapy than after completion of the induction course (p = 0.0001). The hTERT level at diagnosis in patients who did not achieve complete hematological remission was significantly higher than that in patients who achieved complete hematological remission (p = = 0.026). The hTERT level after induction therapy was significantly higher in patients who did not achieve complete hematological remission than in patients who achieved complete hematological remission (p = 0.003). CONCLUSION: Our research suggests that the hTERT expression could serve as a prognostic marker for AML patients. 

scholarly journals Induction of hTERT Expression and Telomerase Activity by Estrogens in Human Ovary Epithelium Cells

2000 ◽  
Vol 20 (11) ◽  
pp. 3764-3771 ◽  
Author(s):  
Silvia Misiti ◽  
Simona Nanni ◽  
Giulia Fontemaggi ◽  
Yu-Sheng Cong ◽  
Jianping Wen ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Molecular Mechanisms ◽  
Estrogen Receptor Α ◽  
Telomerase Activity ◽  
Human Ovary ◽  
Htert Gene ◽  
Human Telomerase

ABSTRACT In mammals, molecular mechanisms and factors involved in the tight regulation of telomerase expression and activity are still largely undefined. In this study, we provide evidence for a role of estrogens and their receptors in the transcriptional regulation of hTERT, the catalytic subunit of human telomerase and, consequently, in the activation of the enzyme. Through a computer analysis of the hTERT 5′-flanking sequences, we identified a putative estrogen response element (ERE) which was capable of binding in vitro human estrogen receptor α (ERα). In vivo DNA footprinting revealed specific modifications of the ERE region in ERα-positive but not ERα-negative cells upon treatment with 17β-estradiol (E2), indicative of estrogen-dependent chromatin remodelling. In the presence of E2, transient expression of ERα but not ERβ remarkably increased hTERT promoter activity, and mutation of the ERE significantly reduced this effect. No telomerase activity was detected in human ovary epithelial cells grown in the absence of E2, but the addition of the hormone induced the enzyme within 3 h of treatment. The expression of hTERT mRNA and protein was induced in parallel with enzymatic activity. This prompt estrogen modulation of telomerase activity substantiates estrogen-dependent transcriptional regulation of the hTERT gene. The identification of hTERT as a target of estrogens represents a novel finding which advances the understanding of telomerase regulation in hormone-dependent cells and has implications for a potential role of hormones in their senescence and malignant conversion.

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