• Title, Summary, Keyword: human telomerase reverse transcriptase

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Immunohistochemistry of Human Telomerase Reverse Transcriptase in Head and Neck Squamous Cell Carcinoma and Resection Margin (두경부 편평상피세포암과 절제연에서 Human Telomerase Reverse Transcriptase의 발현)

  • Kim Yong-Bum;Rho Kyung-Sup;Hong Nam-Pyo;Ahn Hwoe-Young;Lee Yong-Sik;Song Young-Ho
    • Korean Journal of Head & Neck Oncology
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    • v.18 no.1
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    • pp.18-22
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    • 2002
  • Background and Objectives: The expression of telomerase, a ribonucleoprotein complex, has been detected in tissues from many human cancers, but not in the majority of normal tissues except germ cell. It is believed that the activation of telomerase is linked to celluar immortality and may playa role in tumorigenesis. Human telomerase reverse transcriptase (hTERT) has been identified as a putative catalytic subunit of human telomerase and its expression is closely correlated with telomease activity. We studied the expression of hTERT in head and neck squamous cell carcinoma (HNSCC) and resection margin by immunohistochemistry for hTERT and evaluate the correlation between hTERT expression and clinical data in HNSCC. Materials and Methods: We performed a immunohistochemistry in 17 cases of HNSCC and 10 cases of resection margins, histologically normal. The correlations between the hTERT expression and the clinical data in HNSCC were analyzed. Result: hTERT immunoreactivities were detected in 14 of 17 (82.4%) HNSCC, 1 of 10 (10%) resection margin. No correlation was observed between clinical data and hTERT expression in HNSCC. Conclusion: hTERT is activated in HNSCC and its expression is independent from clinical data of patients.

Induction of S Phase Arrest of the Cell Cycle by Piceatannol is Associated with Inhibition of Telomerase Activity in Human Leukemic U937 Cells (Piceatannol에 의한 인체 혈구암세포의 증식 억제 및 telomerase 활성 저하)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.18 no.1
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    • pp.96-102
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    • 2008
  • Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the anti-cancer potency of piceatannol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail. In the present study, we investigated further possible mechanisms by which piceatannol exerts its anti-proliferative action in cultured human leukemia U937 cells. Exposure of U937 cells to piceatannol resulted in growth inhibition and induction of apoptosis as measured by MTT assay and flow cytometry analysis, which was associated with S phase arrest of the cell cycle. Piceatannol treatment markedly inhibited the activity of telomerase, and the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1), main determinants of the telomerase enzymatic activity, were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. However, the levels of cyclooxygenases (COXs) expression and prostaglandin E2 (PGE2) release were not changed in piceatannol-treated U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of piceatannol.

Inhibition of Telomerase Activity in U937 Human Monocytic Leukemia Cells by Compound K, a Ginseng Saponin Metabolite

  • Kang Kyoung-Ah;Lee Kyoung-Hwa;Chae Sung-Wook;Kim Jeong-Ki;Seo Jung-Yeon;Ham Yong-Ho;Lee Kee-Ho;Kim Bum-Joon;Kim Hee-Sun;Kim Dong-Hyun;Hyun Jin Won
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.1
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    • pp.7-12
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    • 2006
  • Telomerase activation is detected in most cancerous cells; hence, telomerase is a highly selective target for cancer therapy, which plays an important role in the apoptotic process. We have previously reported that the ginseng saponin metabolite, Compound K (20-O-D-glucopyranosyl-20(S)-protopanaxadiol, IH901), inhibits cell proliferation by inducing apoptosis and cell cycle arrest at the $G_1$ phase. The present study investigated the regulation of telomerase activity in Compound K treated U937 cells. Compound K treatment caused a reduction in telomerase activity and down-regulated the human telomerase reverse transcriptase (hTERT) gene, resulting in the decreased expressions of its protein, and of the c-Myc and Spl proteins (transcription factors of hTERT). These results indicate that the anticancer activity of Compound K could be mediated by inhibition of the telomerase activity.

Peroxisome proliferator-activated receptor ${\gamma}$ agonist suppresses human telomerase reverse transcriptase expression and aromatase activity in eutopic endometrial stromal cells from endometriosis

  • Chang, Hye Jin;Lee, Jae Hoon;Hwang, Kyung Joo;Kim, Mi Ran;Yoo, Jung Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.40 no.2
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    • pp.67-75
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    • 2013
  • Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

Prognostic Relevance of Human Telomerase Reverse Transcriptase (hTERT) Expression in Patients with Gall Bladder Disease and Carcinoma

  • Deblakshmi, Raj Kumari;Deka, Manab;Saikia, Anjan Kumar;Sharma, Bir Kumar;Singh, Nidhi;Das, NN;Bose, Sujoy
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2923-2928
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    • 2015
  • Background: Gallbladder carcinoma (GBC) has been stated as an Indian disease, with the highest number of cases being reported from certain districts of northeast India, which has an ethnically distinct population. Unfortunately there are no scientific reports on the underlying molecular mechanisms associated with the pathogenesis of the disease from this region. Aim: The present study evaluated the role of differential expression of human telomerase reverse transcriptase (hTERT) in the development of gall bladder anomalies. Materials and Methods: Blood and tissue samples were collected from patients undergoing routine surgical resection for clinically proven cases of gallbladder disease {cholelithiasis (CL, n=50), cholecystitis (CS, n=40) and GBC (n=30) along with adjacent histopathologically proved non-neoplastic controls (n=15)} with informed consent. Whole blood was also collected from age and sex matched healthy controls (n=25) for comparative analysis. Differential hTERT mRNA expression was evaluated by semi-quantitative rt-PCR and real-time PCR based analysis using ${\beta}$-actin as an internal control. Evaluation of differential hTERT protein expression was studied by Western blot analysis and immunoflourescence. Statistical analysis for differential expression and co-relation was performed by SPSSv13.0 software. Results: Gallbladder anomalies were mostly prevalent in females. The hTERT mRNA and protein expression increased gradiently from normal

Antiproliferative Effects of Celecoxib in Hep-2 Cells through Telomerase Inhibition and Induction of Apoptosis

  • Zhao, Yong-Qiang;Feng, Hui-Wei;Jia, Tao;Chen, Xue-Mei;Zhang, Hui;Xu, An-Ting;Zhang, Hai-Ling;Fan, Xian-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4919-4923
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    • 2014
  • Background: To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells). Materials and Methods: The growth inhibition rate of Hep-2 cells in vitro was measured by MTT assay, and apoptosis by TUNEL assay and flow cytometry (FCM). The TRAP-ELISA method was used to determine telomerase activity in Hep-2 cells. The mRNA expression of human telomerase RNA component(hTR), human telomerase reverse transcriptase (hTERT) and human telomerase-associated protein(hTEP1) was determined by RT-PCR assay. Expression of Bax and Bcl-2 proteins was assessed by Western blotting. Results: Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease hTERT mRNA and Bcl-2 protein expression and increase Bax protein expression, PGE2 had no effect on telomerase. Conclusions: Celecoxib had the antiproliferative and pro-apoptotic effect in Hep-2 cells. Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2. Bcl-2 may thus play an important role in telomerase activity as well as apoptosis.

An RNA Mapping Strategy to Identify Ribozyme-Accessible Sites on the Catalytic Subunit of Mouse Telomerase

  • Song, Min-Sun;Lee, Seong-Wook
    • Genomics & Informatics
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    • v.5 no.1
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    • pp.32-35
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    • 2007
  • Telomerase reverse transcriptase (TERT) is an enzymatic ribonucleoprotein that prolongs the replicative life span of cells by maintaining protective structures at the ends of eukaryotic chromosomes. Telomerase activity is highly up-regulated in 85-90% of human cancers, and is predominately regulated by hTERT expression. In contrast, most normal somatic tissues in humans express low or undetectable levels of telomerase activity. This expression profile identifies TERT as a potential anticancer target. By using an RNA mapping strategy based on a trans-splicing ribozyme library, we identified the regions of mouse TERT (mTERT) RNA that were accessible to ribozymes. We found that particularly accessible sites were present downstream of the AUG start codon. This mTERTspecific ribozyme will be useful for validation of the RNA replacement as cancer gene therapy approach in mouse model with syngeneic tumors.