Human Telomerase Reverse Transcriptase (hTERT): A Target Molecule for the Treatment of Cisplatin-resistant Tumors / 대한진단검사의학회지
The Korean Journal of Laboratory Medicine
;
: 430-437, 2008.
Artigo
em Inglês
| WPRIM
| ID: wpr-97400
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Inibidores de Cisteína Proteinase
/
Cisplatino
/
Telomerase
/
Resistencia a Medicamentos Antineoplásicos
/
Caspases
/
Grupo dos Citocromos c
/
RNA Interferente Pequeno
/
Linhagem Celular Tumoral
/
Proteína X Associada a bcl-2
/
Clorometilcetonas de Aminoácidos
Tipo de estudo:
Guia de Prática Clínica
Limite:
Humanos
Idioma:
Inglês
Revista:
The Korean Journal of Laboratory Medicine
Ano de publicação:
2008
Tipo de documento:
Artigo
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