Humans ; Metabolic Syndrome ; Telomerase ; metabolism ; Telomere

Telomerase reverse transcriptase (TERT) is the protein component of telomerase and combined with an RNA molecule, telomerase RNA component, forms the telomerase enzyme responsible for telomere elongation. Telomerase is essential for maintaining telomere length from replicative attrition and thus contributes to the preservation of genome integrity. Although diverse mouse models have been developed and studied to prove the physiological roles of telomerase as a telomere-elongating enzyme, recent studies have revealed non-canonical TERT activities beyond telomeres. To gain insights into the physiological impact of extra-telomeric roles, this review revisits the strategies and phenotypes of telomerase mouse models in terms of the extra-telomeric functions of telomerase.
Animals ; Mice ; Mice, Knockout ; Telomerase/genetics/*metabolism ; Telomere/metabolism

OBJECTIVETo study the frequency of telomerase gene (TERC and TERT) mutation in Northern Chinese patients with acquired bone marrow failure syndromes (BMFS).

METHODSDNA extracted from blood samples of 90 patients with BMFS (including AA, MDS, and PNH) and 45 normal controls from 4 northern hospitals was collected. TERC and TERT mutation analysis was performed by PCR.

RESULTSTwo TERC mutations (n37 A-->G, and n66 G-->C) and two TERT mutations \[n1870 G-->T (E/*)\]; and \[n1780 G-->T (S/I)\] were identified in 90 BMFS patients. Among them, 3 mutations were reported for the first time. One patient with TERT mutation, however, was finally diagnosed as DKC instead of acquired AA, making the incidence of telomerase gene mutation in northern Chinese people with acquired BMFS 3.4%, similar to that of the western country people.

CONCLUSIONThe incidence of telomerase gene mutation in northern Chinese people with acquired bone marrow failure syndromes is 3.4%, similar to that of the western country people.

DNA Mutational Analysis ; Humans ; Mutation ; RNA ; genetics ; Syndrome ; Telomerase ; metabolism

OBJECTIVETo study the oncogene transcriptor c-myc, stimulatory protein 1 (SP1) expression in ameloblastoma (AB) and their relation with telomerase reverse transcripase (hTERT), and to investigate the clinical biological characteristics of AB.

METHODSThe expression was observed in AB by in situ hybridization and SP method.

RESULTSThe positive rates of c-myc mRNA, hTERT mRNA and SP1 protein were 81.5% (44/54), 94.4% (51/54) and 83.3% (45/54), respectively. Their positive rates increased as AB recurred and transformed malignantly. A strong correlation was found between hTERT and c-myc, hTERT and SP1 (rs = 0.853, P < 0.001; rs = 0.900, P < 0.001).

CONCLUSIONActivity of telomerase plays an important role in the tumorigenesis development of AB. Increasing of hTERT expression may be related to c-myc and SP1. The expression of these three parameters has a significant correlation with the clinical biological characteristics of AB.

Ameloblastoma ; metabolism ; Humans ; Proto-Oncogene Proteins c-myc ; metabolism ; Sp1 Transcription Factor ; metabolism ; Telomerase ; metabolism

To observe the expression of cyclin D1, hTERT, and telomerase activity in MNC, HL-60, HL-60A and to explore their effects on leukemogenesis and drug-resistance, normal human peripheral blood mononuclear cells, HL-60 cells sensitive to adriamycin and HL-60A cells resistant to adriamycin were investigated. The cell cycle was analyzed by flow cytometry, and the apoptosis was analyzed by Annexin V-FITC(+) PI staining. Expressions of cyclin D1 and hTERT were determined by real-time PCR and Western blot. Telomerase activity was detected by TRAP-ELISA. The results indicated that the percentage of MNC, HL-60 and HL-60A in S phase was (10.21 + 2.11)%, (44.93 + 3.00)%, and (51.38 + 1.10)% respectively; the percentage of apoptosis cells was (16.14 + 2.13)%, (7.53 + 0.92)%, (4.15 + 0.96)% respectively; the expression of mRNA and protein for cyclin D1 and hTERT increased; the telomerase activities of HL-60 and HL-60A were higher (p = 0.000), whereas the difference between HL-60 and HL-60A was no statistically significant (p = 0.232); positive correlation between cyclin D1, hTERT and telomerase activity had been found (p < 0.01). It is concluded that the cells of S phase increased while the apoptotic cells decreased in HL-60 and HL-60A, especially in HL-60A, which may be due to the up-regulation of cyclin D1, hTERT and telomerase activity.
Cell Cycle ; Cyclin D1 ; metabolism ; HL-60 Cells ; Humans ; Leukemia ; metabolism ; Telomerase ; metabolism

Pluripotent stem cells (PSCs) have the potential to produce any types of cells from all three basic germ layers and the capacity to self-renew and proliferate indefinitely in vitro. The two main types of PSCs, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), share common features such as colony morphology, high expression of Oct4 and Nanog, and strong alkaline phosphatase activity. In recent years, increasing evidences suggest that telomere length represents another important internal factor in maintaining stem cell pluripotency. Telomere length homeostasis and its structural integrity help to protect chromosome ends from recombination, end fusion, and DNA damage responses, ensuring the divisional ability of mammalian cells. PSCs generally exhibit high telomerase activity to maintain their extremely long and stable telomeres, and emerging data indicate the alternative lengthening of telomeres (ALT) pathway may play an important role in telomere functions too. Such characteristics are likely key to their abilities to differentiate into diverse cell types in vivo. In this review, we will focus on the function and regulation of telomeres in ESCs and iPSCs, thereby shedding light on the importance of telomere length to pluripotency and the mechanisms that regulate telomeres in PSCs.
Animals ; Humans ; Models, Biological ; Pluripotent Stem Cells ; metabolism ; Telomerase ; metabolism ; Telomere ; metabolism ; Telomere Homeostasis

OBJECTIVETo investigate the proportion between tumors which maintain their telomeres by a mechanism of alternative lengthening of telomeres(ALT) and telomerase-dependent tumors in gastrointestinal malignant tumors, the expression difference of hRad21 between the two groups and the clinicopathological characteristics of ALT tumors were also explored.

METHODSOne hundred and four cases of gastrointestinal malignant tumors were divided into 2 groups: ALT group and telomerase group by detecting telomerase activity using TRAP method. Expression difference of hRad21 was investigated between the two groups. All the patients were followed up and clinicopathological data of these patients were analyzed.

RESULTSOf 104 cases, there were 12 cases in ALT group and 94 cases in telomerase group. Expression of hRad21 in ALT group was higher than that in telomerase group. Tumors in ALT group had a thinner invasion depth (lower T stage) as compared to telomerase group (P=0.021). Other indexes, such as age, gender, tumor size, tumor grade, location of tumor, CEA and CA199, were not significantly different between the two groups. Results of follow-up showed that the survival rate of ALT group was 100% while that of telomerase group was 56% at 30 months postoperatively.

CONCLUSIONSThere are tumors which maintain their telomeres by ALT in gastrointestinal malignant tumors, accounting for 10%-12% of the total tumors. As compared to telomerase group, ALT group presents higher expression of hRad21, thinner tumor invasion depth, and higher survival rate.

Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; Humans ; Male ; Neoplasm Invasiveness ; Nuclear Proteins ; metabolism ; Phosphoproteins ; metabolism ; Telomerase ; metabolism ; Telomere ; metabolism

OBJECTIVETo study the expression of hTERT mRNA and Mad1 protein in lung cancer of Gejiu and Xuanwei and normal lung tissue and to investigate their correlations with lung cancer.

METHODSMad1 protein was detected by immunohistochemistry S-P method, and hTERT message RNA (mRNA) was detected by in situ hybridization (ISH) in 40 specimens of lung cancer of Gejiu Tin miners and 20 specimens of lung cancer of Xuanwei peasants and 20 specimens of normal lung tissue. The positive signals were quantitatively analyzed by HPIAS-100.

RESULTSThe positive unit (PU) of Mad1 protein was 16.77 +/- 6.01 in Gejiu Tin Miners lung cancer group, and 19.36 +/- 4.54 in Xuanwei peasant lung cancer group, compared with the normal lung tissue (46.05 +/- 7.26). The difference was highly significant (P < 0.01); The PU of hTERT mRNA was 72.10 +/- 13.07 in Gejiu Tin miners lung cancer group, and 74.20 +/- 15.17 in Xuanwei peasant lung cancer group, which was higher than that in normal tissue group (10.70 +/- 2.21). The difference was significant (P < 0.01). The expression of Mad1 protein was negatively correlated with the expression hTERT mRNA (P < 0.05, r = 0.9881, r = -0.999).

CONCLUSIONReduced hTERT mRNA expression may play an important role in the occurrence of lung cancer. The expression of hTERT mRNA and deletion of Mad1 protein are closely related to pathogenesis of lung cancer.

Cell Cycle Proteins ; metabolism ; China ; Female ; Humans ; Lung ; metabolism ; Lung Neoplasms ; metabolism ; Male ; Mining ; Nuclear Proteins ; metabolism ; Telomerase ; metabolism

With the smooth move towards the coming expected clinical reports of anticancer pharmaceutical molecules targeting telomeres and telomerase, and also with the exciting success in the extension of lifespan by regulating telomerase activity without increased onset of oncogenesis in laboratory mouse models (Garcia-Cao et al., 2006; Jaskelioff et al., 2011), we are convinced that targeting telomeres based on telomerase will be a potential approach to conquer both aging and cancer and the idea of longevity seems to be no more mysterious. More interestingly, emerging evidences from clinical research reveal that other telomeric factors, like specific telomeric binding proteins and nonspecific telomere associated proteins also show crucial importance in aging and oncogenesis. This stems from their roles in the stability of telomere structure and in the inhibition of DNA damage response at telomeres. Uncapping these proteins from chromosome ends leads to dramatic telomere loss and telomere dysfunction which is more abrupt than those induced by telomerase inactivation. Abnormal expression of these factors results in developmental failure, aging and even oncogenesis evidenced by several experimental models and clinical cases, indicating telomere specific proteins and its associated proteins have complimentary roles to telomerase in telomere protection and controlling cellular fate. Thus, these telomeric factors might be potential clinical biomarkers for early detection or even therapeutic targets of aging and cancer. Future studies to elucidate how these proteins function in telomere protection might benefit patients suffering aging or cancer who are not sensitive to telomerase mediation.
Aging ; Biomarkers ; metabolism ; Humans ; Longevity ; Neoplasms ; metabolism ; pathology ; Telomerase ; metabolism ; Telomere ; metabolism ; ultrastructure ; Telomeric Repeat Binding Protein 2 ; metabolism

OBJECTIVETo measure telomere length of patients with bone marrow failure syndrome (BMFS) and explore the relationship between telomerase gene mutation and telomere shortening.

METHODSBlood samples from 10 patients with AA, MDS-RA were collected and performed TERC and TERT gene mutation analysis. Telomere length was measured by Southern blot and compared with normal controls and two patients with MDS-RAEB and AML each.

RESULTSTwo patients in the 10 BMFS patients had TERC and TERT gene mutations and very short telomeres compared with normal controls and with the 8 BMFS counterparts, the telomere length was less than 50% of that of normal control, and was similar to that of patients with MDS-RAEB and acute myelogenous leukemia, indicating the possibility of malignant transformation. Some BMFS patients with no mutations also had short telomeres.

CONCLUSIONSBMFS patients with telomerase gene mutation have very short telomeres, being similar to that of hematological malignancies. Some BMFS patients with no telomerase gene mutations also have short telomere length.

Asian Continental Ancestry Group ; Humans ; Mutation ; Pancytopenia ; Telomerase ; metabolism ; Telomere ; metabolism