Assessment of telomerase as drug target in breast cancer

Telomerase is a specialized enzyme which maintains telomere length at the extreme end of the chromosome.Over 90% of all cases of cancer show high expression of telomerase while in normal cells, its expression isextremely low or undetectable. Detection of telomerase activity in a wide range of breast cancer makestelomerase an interesting target for diagnosis and therapy. In this review, we have aimed to describe telomeraseas a therapeutic and accurate diagnostic target in breast cancer. Telomerase performs many extracurricularactivities apart from maintaining telomere length; here, we have also tried to address its role in epithelialmesenchymal transition (EMT) of breast cancer progression.

Activity of Telomerase in Coal Worker's Autopsied Lung / 대한산업의학회지

OBJECT: We measured the activity of telomerase in coal workers lung tissue and found a significant increase in telomerase activity compared to the control group. Pneumoconiosis has the characteristics of fibroblast proliferation and the accumulation of collagen,thus finally causing the pathologic changes,which lead to the irreversible and progressive fibrosis of the lungs. We hypothesized that this cellular proliferation causing irreversible fibrosis may induce some elongation of the life cycle in the chromosomes and lead to further cellular immortalization. METHOD: 8 postmortem(within 24 hours)pneumo-coniotic cases were examined and their telomerase activity was compared with that of the autopsied lungs of lung cancer patients and of accident victims without any respiratory diseases. Using the extracted ribo-nucleoprotein from pneumoconiotic nodules, telomeric repeat amplification assay (TRAP)was done. RESULT: The pneumoconiotic lungs showed strong telomerase activity, similar to that of the lung cancer patients, while the control group showed no such activity. CONCLUSION: Based on the results of this study, we found that coal dust-induced cellular proliferation affects telomerase-activity clinically.

Pattern of Telomerase Activities in Acute Leukemias and Chronic Myeloid Leukemia / 대한혈액학회지

BACKGROUND: Telomerase has a leading role as a potential enzyme responsible for tumorigenesis and longevity. Telomerase is a ribonucleoprotein that synthesizes a specific repeating nucleotide sequence onto the ends of telomeres. This enzyme is normally present in immortalized cell lines, germ-line tissues, and tumor tissues. We intended to compare the telomerase activity among various types of leukemia to determine the association of telomerase activity and patients status and responsiveness of chemotherapy. METHODS: Specimens were collected from Jan. 1999 to Oct. 1999 and included the leukemic bone marrow (ALL, AML and CML) and the peripheral blood or bone marrow of normal persons or patients with iron deficiency anemia and immune thrombocytopenic purpura. Telomerase activity was measured by TRAP assay using Telomerase PCR ELISA kit. RESULTS: Telomerase activities were increased in acute leukemias and relapsed acute leukemia cases, whereas in the cases of complete remission state of acute leukemia, the activity was decreased. Telomerase activity was increased in leukemias which had high percentage of immature cells, especially more than 70% of blast. Also the activity was decreased in post-chemotherapeutic group, whereas increased in untreated group. There was no significant difference between prognosis of chromosomal abnormalities and telomerase activity. CONCLUSION: These results showed that telomerase activity was increased in acute phase of leukemia, high percentage of immature cells, and chemoresistant group of leukemia.

Association between Telomerase Activity, Cell Cycle Regulators, and Histopathological Prognostic Parameters in Breast Cancer

PURPOSE: Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto the ends of chromosomes, thereby preventing the replication-dependent shortening of those ends. This enzyme is essential for stability of eukaryotic chromosomes and may be necessary for cell immortalization. Telomerase activity is detected in a wide range of cancers of various tissues, and its expression may be a critical step in tumor progression. METHODS: The telomerase activity was measured using a telomeric repeat amplification protocol (TRAP) assay in 65 cases of breast cancers, 9 cases of fibroadenomas, and 7 cases of normal breast tissues. To compare the telomerase activity with cell cycle regulators, we measured the expression of the cyclin D1 and the p53 proteins by using immunohistochemical analysis. To compare the telomerase activity with traditional prognostic indicators, we measured the ER, PR, c-erbB-2 and ki-67 expression by using immunohistochemical analysis. Disease-free survival and overall survival in relation to telomerase activity were studied by using the Kaplan-Meier method. RESULTS: Telomerase activity was detected in 42 (64.6%) of the 65 breast cancers, 4 (44.4%) of the 9 fibroadenomas, and in none of the 7 normal breast tissues. There was no significant relationship between telomerase activity and cell cycle regulators such as cyclin D1 or p53. There was no statistical correlation between telomerase activity and tumor size, lymph nodal status, or histopathological prognostic parameters, such as ER, PR, p53, c-erbB-2 and ki-67, but a significant correlation was found (p=0.006) between telomerase activity and histologic grade. The telomerase activity was not significantly correlated with either the overall survival or the disease-free survival. CONCLUSION: These results suggest that telomerasemay play a role in the malignant transformation of breast tissue and that this enzyme was more activated in cancers of a poor histologic grade. However, the telomerase activity was not related to cell cycle regulators and traditional prognostic parameters. The possible significance of telomerase activity in breast cancer remains open to further investigation.

Telomerase Activity in Musculoskeletal Tumors / 대한정형외과연구학회지

Telomerase activity has been detected in many human immortal cell lines and tumor tissues. We studied telomerase activity in a series of human musculoskeletal tumors. Twenty-eleven tumors from 27 patients were studied using a sensitive PCR (polymerase chain reaction)-based technique, the TRAP(telomeric repeat amplication protocol) assay. Telomerase activity was present in seven tumors(25.9%). Telomerase activity was present in six of 18 malignant tumors(33.3%), while telomerase was active in one of 9 benign tumors(11.1%). Telomerase was active in 40% for osteosarcomas, 25% for soft tissue sarcomas, 16.7% for giant cell tumors of bone, and none for benign tumors. These results are a remarkablely low positive rate of telomerase activity in comparing with other types of carcinoma. In conclusion, it suggests that the musculoskeletal tumors, arisen from mesenchymal cells, follow different pathways of neoplastic progression or it is due to tile specific characteristics stick of sarcomas-abundant extracellular matrix and lack of tumor cells-differed tumor those of carcinomas.