Human Telomerase Reverse Transcriptase (hTERT): A target molecule for the treatment of cisplatin-resistant tumors

Yuk Pheel Park, Kwang Dong Kim, Seong Ho Kang, Do Young Yoon, Joo Won Park, Jong Wan Kim, Hee Gu Lee

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)430-437
Number of pages8
JournalKorean Journal of Laboratory Medicine
Volume28
Issue number6
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • Apoptosis
  • Bladder cancer
  • Caspase
  • Cisplatin
  • hTERT

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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