Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes

Abstract

Human telomerase consists of two essential components, telomerase RNA template (hTER) and telomerase reverse transcriptase (hTERT), and functions to synthesize telomere repeats that serve to protect the integrity of chromosomes and to prolong the replicative life span of cells. Telomerase activity is expressed selectively in germ-line and malignant tumor cells but not in most normal human somatic cells. As a notable exception, telomerase is expressed in human lymphocytes during development, differentiation, and activation. Recent studies have suggested that regulation of telomerase is determined by transcription of hTERT but not hTER. The highly regulated expression of telomerase in lymphocytes provides an opportunity to analyze the contribution of transcriptional regulation of hTERT and hTER. We report here an analysis of hTERT expression by Northern and in situ hybridization. It was found that hTERT mRNA is expressed at detectable levels in all subsets of human lymphocytes isolated from thymus, tonsil, and peripheral blood, regardless of the status of telomerase activity. hTERT expression is regulated as a function of lineage development, differentiation, and activation. Strikingly, however, telomerase activity in these cells is not correlated strictly with the levels of hTERT and hTER transcripts. The absence of correlation between telomerase activity and hTERT mRNA could not be attributed to the presence of hTERT splice variants or to detectable inhibitors of telomerase activity. Thus, transcriptional regulation of hTERT is not sufficient to account for telomerase activity in human lymphocytes, indicating a likely role of posttranscriptional factors in the control of enzyme function.

Telomerase catalytic subunit in laryngeal carcinogenesis—an immunohistochemical study

“…It is well known that, in addition to neoplastic cells, activated lymphocytes do possess low levels of telomerase activity and may influence RT-PCR results. 23 To the best of our knowledge, the present study is the first to analyse systematically the presence of hTERT protein in different morphological grades of laryngeal carcinogenesis, including laryngeal squamous cell carcinomas, by immunohistochemistry.…”

Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications

“…In a subset of our CLL cohort (n ¼ 19), we have analysed the mRNA levels of the catalytic unit of telomerase, hTERT, which have been shown to correlate with the telomerase activity in B lymphocytes (Liu et al, 1999;Norrback et al, 2001). …”

Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFβ

“…In addition, telomerase is expressed in some normal rodent organs having self-renewal properties, such as the liver, spleen, thymus, and testis, even in adult animals (Greider, 1998). This activity has also been found in activated lymphocytes, and more recently in injured and inflamed skin, fibrotic liver, hypertensive blood vessels, and injured lungs undergoing fibrosis (Tahara et al, 1995;Taylor et al, 1996;Tsujiuchi et al, 1998;Liu et al, 1999Liu et al, , 2002Nozaki et al, 2000). Induction of this activity in injured tissues suggests a potential role for telomerase in the repair and/or fibrotic process.…”