Telomerase catalyzes the elongation of telomeric repeat DNA to maintain telomere length and structure (1). Although telomerase is a complex composed of a catalytic subunit (hTERT) and an RNA component (hTER), it is the expression of hTERT (2,3) that is the major determinant of telomerase activity in human cells (1,4). Maintaining telomere length by telomerase is associated with human cell immor...

We report that in endothelial cells, the angiogenic effect of 17beta-estradiol (E2) is inhibited by the estrogen receptor (ER) antagonist ICI or the NO synthase (NOS) inhibitor 7-nitroindazole via downregulation of hTERT, the telomerase catalytic subunit, suggesting that E2 and NO are involved in controlling hTERT transcription. Quantitative Real-Time PCR and chromatin immunoprecipitations in E...

BACKGROUND Human telomerase reverse transcriptase (hTERT) has become an ideal target for development of anticancer therapy. Small interfering RNAs (siRNAs) are very powerful reagents for gene silencing and show promise for cancer gene therapy. However, only a small number of siRNAs have been demonstrated to be effective. For gene therapy targeting hTERT, it is essential to develop a robust syst...

Treatment of advanced ovarian cancer involves platinum-based chemotherapy. However, chemoresistance is a major obstacle. Cancer stem cells (CSCs) are thought to be one of the causes of chemoresistance, but the underlying mechanism remains elusive. Recently, human telomerase reverse transcriptase (hTERT) has been reported to promote CSC-like traits. In this study, we found that a mitotic inhibit...

Telomerase, an enzymatic activity responsible for the replication of chromosome end structures, is strongly upregulated in most human cancers. In contrast, most differentiated tissues are telomerase negative. The rate-limiting step for telomerase activity seems to be the expression of the catalytic subunit of the enzyme, encoded by the human telomerase reverse transcriptase (hTERT) gene. The pr...

BACKGROUND Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported...

Indole-3-carbinol (I3C), a naturally occurring hydrolysis product of glucobrassicin from cruciferous vegetables such as broccoli, cabbage and Brussels sprouts, is an anticancer phytochemical that triggers complementary sets of antiproliferative pathways to induce a cell cycle arrest of estrogen-responsive MCF7 breast cancer cells. I3C strongly downregulated transcript expression of the catalyti...

Telomerase, the enzyme that synthesizes telomeric DNA, is not expressed in most human somatic cells but is activated with in vitro immortalization and during tumorigenesis, and repressed by cell differentiation. Of the two components of the core enzyme, the catalytic protein hTERT is limiting for activity. To investigate mechanisms of hTERT gene regulation, we have cloned genomic sequences enco...

Resistance to gemcitabine is the major problem in pancreatic cancer chemotherapy, and recent evidence suggests that down-regulation of hTERT mRNA could enhance the antitumor efficacy of other well known chemotherapy agents targeting DNA. The aim of this study was to evaluate the combined antitumor efficacy of antisense oligonucleotides (AS-ODN) targeting hTERT mRNA and gemcitabine in human panc...

PURPOSE Elevated levels of human telomerase (hTERT) mRNA in tumors is a marker for poorer survival in patients with stage I non-small cell lung cancer (NSCLC). A functional variant of MNS16A-short tandem repeats in hTERT (S allele) is associated with higher expression levels of hTERT mRNA compared with the MNS16A-long (L) allele. It is unknown, however, whether or not the hTERT MNS16A variant g...