Quantitative telomerase activity in malignant, benign and normal gynecological tissues.
ABSTRACT The aim of this study was to evaluate quantitative telomerase activity in malignant, benign and normal gynecological tissue samples by using the Telomerase-PCR ELISA kit, and to determine a cut-off level for malignancy by this quantitative method.
Fifty gynecological tumors, 27 benign gynecological disorders and 29 normal tissues were analyzed by the Telomerase-PCR ELISA kit. All tissues were confirmed by a pathologist. A ROC (receiver operator characteristic) curve was drawn to determine a threshold level best discriminating malignant tissues from benign pathologies and normal tissues. Telomerase activity was compared in malignant, benign and normal tissues.
The mean level of telomerase activity of the malignant tumor samples (1.03 +/- 0.53 units) was significantly (p < .001) higher than the normal tissues (0.13 +/- 0.07 units) and benign pathologies (0.37 +/- 0.25 units). The cut-off point to differentiate malignant samples from benign samples was set at 0.42 units, where the sensitivity was 93.8% and the specificity was 89.3%. Positive predictive value was 84% and negative predictive value was 89.3%. There was a significant difference in telomerase activity between malignant, benign and normal tissues within each histological group.
In this preliminary study, the telomerase-PCR ELISA method was found to have a high sensitivity and specificity to differentiate malignant gynecological tissues from benign tissues.
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ABSTRACT: Activation of telomerase is a key element in oncogenesis and resistance to apoptosis for many cancers. Some histone deacetylase inhibitors (HDACi) or chemotheraputic agents have been reported to downregulate the expression of human telomerase reverse transcriptase (hTERT). However, whether hTERT is involved in cell death of uterine cancer cells induced by combination of HDACi with chemotheraputic regents remain unknown. The present study shows that combining sodium butyrate (NaBu) and adriamycin (ADR) inhibits proliferation of uterine cancer cell lines in a concentration and time-dependent manner. Growth inhibition was accompanied by caspase-dependent apoptosis with reduced telomerase activity and decreased hTERT mRNA expression. Ectopic wild type (WT)-hTERT suppressed the apoptosis induced by NaBu/ADR treatment, while knockdown of hTERT sensitized uterine cancer cells to ADR. Moreover, the addition of NaBu significantly enhanced ADR cytotoxicity for the primary uterine cancer cells with high hTERT expression. These data indicate that downregulation of hTERT is an important part of the mechanism by which NaBu enhances ADR-induced apoptosis, and suggests that combining NaBu and ADR may be effective in treating uterine tumor with high telomerase activity. © 2013 Wiley Periodicals, Inc.Molecular Carcinogenesis 07/2014; 53(7). DOI:10.1002/mc.21998 · 4.77 Impact Factor
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ABSTRACT: Background: Telomeres are essential for the function and stability of eukaryotic chromosomes. Telomerase consists of three subunits: human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and telomerase protein 1 (TP1). The hTERT subunit determines the activity of telomerase as an enzyme and is detected in most human tumors and regenerative cells. Telomerase activity is a useful cancer-cell detecting marker in some types of cancers. Aims: The aim of this study was to assess of telomerase hTERT mRNA in gynaecological tumors for diagnosis of malignancy. Study Design: Cross-sectional study. Methods: A total of 55 gynaecologic tumor samples (35 ovarian, 13 endometrial, 6 cervical and 1 placental site trophoblastic tumor tissue) were obtained at the time of surgery. Quantification of hTERT mRNA was performed in a real-time reverse transcriptase polymerase chain reaction (RT-PCR) using the LightCycler TeloTAGGG hTERT Quantification Kit. Results: It was histopathologically detected that 18 of the tissue samples were malignant and 37 of the samples were benign. 16 of the malignant tissue samples (88.9%) and 3 (8.1%) (endometrial tissue in proliferative phase, mucinous cyst adenoma and endometriosis) of the benign tissue samples were found to be hTERT positive. With the presence of these data, sensitivity and specificity of hTERT for the diagnosis of malignancy were calculated to be 88.9% and 91.9%, respectively. Conclusion: It was suggested that the measurement of telomerase activity in gynaecologic tumors, except for endometrial tissue in the reproductive phase, is a valuable method for pathological investigation.Balkan Journal of Medical Genetics 09/2013; 30(3):287-92. DOI:10.5152/balkanmedj.2013.7328 · 0.17 Impact Factor