Human telomerase reverse transcriptase (hTERT): a target molecule for the treatment of cisplatin-resistant tumors = Human telomerase reverse transcriptase (hTERT): cisplatin-내성 암의 치료를 위함 목적 단백질

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Title
Human telomerase reverse transcriptase (hTERT): a target molecule for the treatment of cisplatin-resistant tumors = Human telomerase reverse transcriptase (hTERT): cisplatin-내성 암의 치료를 위함 목적 단백질
Author(s)
Y P Park; K D Kim; S H Kang; D Y Yoon; J W Park; J W Kim; Hee Gu Lee
Bibliographic Citation
Korean Journal of Laboratory Medicine, vol. 28, no. 6, pp. 430-437
Publication Year
2008
Abstract
BACKGROUND: Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme that is required for telomerase activity (TA) and cancer progression. Telomerase inhibition or inactivation increases cellular sensitivity to UV irradiation, DNA-damaging agents, the tyrosine kinase inhibitor, imatinib, and pharmacological inhibitors, such as BIBR1532. hTERT is associated with apoptosis. Some patients show drug-resistance during anti-cancer drug treatment and the cancer cell acquire anti-apoptotic mechanism. Therefore, we attempted to study correlation between hTERT and drug-resistance. METHODS: To study the correlation between protein level and activity of hTERT and drug-resistance, Western blotting and telomerase repeat amplification protocol (TRAP) assays were performed. To investigate whether hTERT contributes to drug resistance in tumor cells, we transiently decreased hTERT levels using small interfering RNA (siRNA) in T24/R2 cells. RESULTS: hTERT knockdown increased Bax translocation into the mitochondria and cytochrome C release into the cytosol. Caspase inhibitors, especially Z-VAD-FMK, rescued this phenomenon, suggesting that the stability or expression of hTERT might be regulated by caspase activity. CONCLUSIONS: These data suggest that hTERT might be a target molecule for drug-resistant tumor therapy.
Keyword
ApoptosisBladder cancerCaspaseCisplatinhTERT
ISSN
I000-0170
Publisher
South Korea
DOI
http://dx.doi.org/10.3343/kjlm.2008.28.6.430
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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