• Title/Summary/Keyword: Human Telomerase Reverse Transcriptase (hTERT)

Search Result 33, Processing Time 0.032 seconds

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
    • /
    • v.18 no.1
    • /
    • pp.18-22
    • /
    • 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.

Immortalization of Swine Umbilical Vein Endothelial Cells with Human Telomerase Reverse Transcriptase

  • Hong, Hai Xia;Zhang, Yan Ming;Xu, Hao;Su, Zheng Yuan;Sun, Pei
    • Molecules and Cells
    • /
    • v.24 no.3
    • /
    • pp.358-363
    • /
    • 2007
  • Swine endothelial cells are commonly used as an in vitro model for studying features of the blood-brain barrier and some hemorrhagic diseases. However, primary cultures of swine cells have finite lifespans. To establish immortalized swine umbilical vein endothelial cells (SUVECs) using human telomerase reverse transcriptase (hTERT), the plasmid pCI-neo-hTERT was transfected into SUVECs by lipofection. Clones were selected for G418 resistance, and positive clones were amplified. One of the clones was cultured for up to 50 passages. Factor VIII-related antigen and CD34 were detected. The immortalized cells shared the properties of normal cells, such as contact inhibition, serum requirement and anchorage dependence. Karyotype analysis revealed that the immortalized cells were in the diploid range. In addition, both in vivo and in vitro assays of tumorigenicity showed no neoplastic transformation. Furthermore, NO, $PGI_2$, and ET-1 concentrations in the transfected cells were normal. These results suggest that the SUVECs immortalized by hTERT retain their original characteristics.

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
    • /
    • v.16 no.7
    • /
    • pp.2923-2928
    • /
    • 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

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
    • /
    • v.18 no.1
    • /
    • pp.96-102
    • /
    • 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.

Telomerase Reverse Transcriptase Contains a BH3-Like Motif and Interacts with BCL-2 Family Members

  • Jin, Young;You, Long;Kim, Hye Jeong;Lee, Han-Woong
    • Molecules and Cells
    • /
    • v.41 no.7
    • /
    • pp.684-694
    • /
    • 2018
  • Upregulation of human telomerase reverse transcriptase (hTERT) expression is an important factor in the cellular survival and cancer. Although growing evidence suggests that hTERT inhibits cellular apoptosis by telomere-independent functions, the mechanisms involved are not fully understood. Here, we show that hTERT contains a BH3-like motif, a short peptide sequence found in BCL-2 family proteins, and interacts with anti-apoptotic BCL-2 family proteins MCL-1 and BCL-xL, suggesting a functional link between hTERT and the mitochondrial pathway of apoptosis. Additionally, we propose that hTERT can be categorized into the atypical BH3-only proteins that promote cellular survival, possibly due to the non-canonical interaction between hTERT and antiapoptotic proteins. Although the detailed mechanisms underlying the hTERT BH3-like motif functions and interactions between hTERT and BCL-2 family proteins have not been elucidated, this work proposes a possible connection between hTERT and BCL-2 family members and reconsiders the role of the BH3-like motif as an interaction motif.

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
    • /
    • v.40 no.2
    • /
    • pp.67-75
    • /
    • 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.

Diosgenin Inhibits hTERT Gene Expression in the A549 Lung Cancer Cell Line

  • Mohammad, Rahmati Yamchi;Somayyeh, Ghareghomi;Gholamreza, Haddadchi;Majid, Mobasseri;Yousef, Rasmi
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.11
    • /
    • pp.6945-6948
    • /
    • 2013
  • Background: Diosgenin, a steroidal saponin from a therapeutic herb, fenugreek (Trigonellafoenum-graceum L.), has been recognized to have anticancer properties. Telomerase activity is not detected in typical healthy cells, while in cancer cell telomerase expression is reactivated, therefore providing a promising cancer therapeutic target. Materials and Methods: We studied the inhibitory effect of diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT- assays and qRT-PCR analysis were conducted to assess cytotoxicity and hTERT gene expression inhibition effects, respectively. Results: MTT results showed that $IC_{50}$ values for 24, 48 and 72h after treatment were 47, 44 and $43{\mu}M$, respectively. Culturing cells with diosgenin treatment caused down-regulation of hTERT expression. Discussion: These results show that diosgenin inhibits telomerase activity by down-regulation of hTERT gene expression in the A549 lung cancer cell line.

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

  • Song, Min-Sun;Lee, Seong-Wook
    • Genomics & Informatics
    • /
    • v.5 no.1
    • /
    • pp.32-35
    • /
    • 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.