
<ArticleTitle>[<prot>Telomerase</prot>, cell immortality and cancer]</ArticleTitle>
<AbstractText><prot>Telomerase</prot> is an enzyme that replaces repetitive (TTAGGG)n sequences on the ends of chromosomes that would otherwise be lost during successive cell divisions. <prot>Telomerase</prot> activity is closely linked to attainment of cellular immortality, a step in carcinogenesis, while lack of such activity contributes to cellular senescence. <prot>Telomerase</prot> is activated in more than 85% of malignant tumors. However, with the exception of some self-renewing tissues with high regenerative potential, <prot>telomerase</prot> activity is usually repressed in normal somatic tissues. Based on these reports, we investigated <prot>telomerase</prot> activity in gastric mucosal tissues. <prot>Telomerase</prot> activity is highest in cancer, followed by intestinal metaplasia, chronic gastritis, and normal mucosa. In patients with intestinal-type gastric cancer, <prot>telomerase</prot> activity was higher in those with intestinal metaplasia and H. pylori infection than in patients without infection. Our results suggest that H. pylori infection may influence <prot>telomerase</prot> activity in cancer and noncancerous tissue. Genes encoding three major components of human <prot>telomerase</prot> have been recently cloned. They included those for human <prot>telomerase RNA</prot> component (<prot>hTR</prot>), human <prot>telomerase reverse transcriptase</prot> (<prot>hTERT</prot>), and <prot>telomerase-associated protein 1</prot> (<prot>TEP1</prot>). More recently, two human <prot>telomeric repeat binding factor</prot>s (<prot>TRF</prot>s) have also been cloned: <prot>TRF1</prot>, considered to inhibit the action of <prot>telomerase</prot> at the telomeric region, and <prot>TRF2</prot>, believed to prevent fusion of chromosome ends and, in vitro, to remodel linear telomeric DNA into large duplex loops. However, the details of mechanisms regulating <prot>telomerase</prot> activity are still poorly understood, and specific components or binding proteins that might represent suitable targets for cancer gene therapy have not yet been identified. Therefore, we established quantitative assays using a TaqMan RT-PCR for mRNAs encoding the <prot>telomerase</prot> components <prot>hTR</prot>, <prot>hTERT</prot>, and <prot>TEP1</prot>, as well as for those encoding <prot>TRF1</prot> and <prot>TRF2</prot>. By using our quantitative assays, we found the following results: 1) Expression of <prot>TRF1</prot> and <prot>TRF2</prot> mRNA was greater in the normal cells than in human malignant hematopoietic cell lines or in patients with acute leukemia, 2) <prot>hTERT</prot> mRNA expression showed changes paralleling <prot>telomerase</prot> activity and became undetectable with HL60 cell differentiation, 3) initially low expression of <prot>TRF1</prot> and <prot>TRF2</prot> mRNA increased during differentiation. Our results suggest that not only <prot>hTERT</prot> but also <prot>TRF1</prot> and 2 are important regulators of <prot>telomerase</prot> activity.</AbstractText>
